IndraLab

Statements


| 401

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"There are some attractive features of anti CAM-DR strategy."

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"We hypothesized that a decreased level of extracellular COL3A1 resulted in reduced drug binding, increased drug diffusion into cells, and reduced interaction between ECM and cell surface receptors, resulting in reduced CAM-DR strength."

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"The bone marrow environment has been shown to promote cell adhesion-mediated drug resistance (CAM-DR) in leukemia cells, which may contribute to relapse."

sparser
"However, the underlying mechanisms of CAM-DR and the fact of whether and how it interferes with other types of resistance remain to be elucidated."

sparser
"Thus it will be critical to move toward a personalized approach for targeting the CAM-DR phenotype associated with cell adhesion as well as for inhibitors of soluble factors that confer drug resistanc[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"They attribute this to cell adhesion-mediated drug resistance (CAM-DR) and suggest that the interaction of ECM components, including collagen, with the cancer cells results in chemoresistance."

sparser
"These data strongly support that translation of CAM-DR signaling pathway regulators to clinic in combination with standard therapy can be considered as a rational strategy to overcome resistance."

sparser
"Most mechanisms of CAM-DR are not fully understood, possibly due to multifactorial processes involving different molecular players such as cell adhesion molecules and ECM components."

sparser
"As Wnt signaling has been shown to be an aberrantly upregulated pathway in leukemia ( xref ) and is involved with chemoresistance, this warrants further exploration of celecoxib as a viable therapy to reverse CAM-DR in leukemia."

sparser
"It is obvious that SFM-DR and CAM-DR act closely with each other and cannot be separated completely."

sparser
"Nevertheless, CAM-DR has attracted relatively little attention during the last decade despite growing evidence concerning the relevance of CAM-DR for different tumor entities."

sparser
"VTD-PACE is a good option for EMD considering CAM-DR and hypoxia, but might be intolerable for the majority of patients with a terminal phase of MM [ xref ]."

sparser
"To further elucidate the effect of TRPV1 inhibition on stroma-mediated resistance to bortezomib, we evaluated the activation of pro-survival signaling pathways implicated in CAM-DR."

sparser
"Mounting evidence suggests that cell adhesion-mediated drug resistance (CAM-DR), caused by the interaction between the bone marrow microenvironment and tumour cells may play an important role in drug resistance to chemotherapy."

sparser
"To investigate whether the diverse dependency of CAM-DR in W1 and W1CR cells from ITGB1 is manifested in intracellular integrin signaling, we focused on integrin linked kinase (ILK)."

sparser
"Integrins the heterodimeric adhesion that molecules possess, depending on their subunit composition, the capability to bind ECM components further mediating CAM-DR ( xref )."

sparser
"Apart from CXCR4, MM cells also express CXCR7, an alternative receptor of CXCL12, which may also be involved in CAM-DR in MM [ xref ] as well as in MM progression [ xref ]."
| PMC

sparser
"Although CAM-DR is relevant in both cell lines in addition to the existing cisplatin resistance in W1CR cells, the β1-integrin signaling induces different signaling pathways in both cell lines."

sparser
"Again, the combination AUR/BTZ significantly decreased CAM-DR (−17.7% and −29.9% for viability, for the lowest concentration of AUR, comparing cells in suspension vs. on FBN-coated plates)."

sparser
"Studies have shown that MM cells can be protected from chemotherapy-induced apoptosis by the phenomenon called cell adhesion mediated drug resistance (CAM-DR) [ xref ]."

sparser
"In this study, we also construct the CAM-DR model with the co-culture of BMSCs and MM cells."

sparser
"Expression of VLA-4, a member of the integrin superfamily of adhesion receptors that is recognized as a main factor involved in CAM-DR [ xref ], is regulated by Btz treatment in MM cells."

sparser
"For example, the interaction between the tumoral cells and the extracellular matrix (ECM) through the binding with its components (collagen, fibronectin, and laminin) is responsible for the cell adhesion-mediated drug resistance (CAM-DR), that mediates the resistance to radiotherapy and antibody-based receptor tyrosine kinase (RTK) inhibition ( xref , xref )."

sparser
"The focal adhesion pathway, along with CAM-DR has commonly been linked to drug resistance in MM patients xref , due partly to the increased abundance of Wnt3."
| PMC

sparser
"Few studies analyze redundancy between integrins in CAM-DR, and how it might affect integrin targeting."

sparser
"Therefore, it can be stated the more stiffen collagen network the more efficient blocking of drug diffusion [ xref , xref ] and/or more efficient CAM-DR induction."

sparser
"The interaction between MM plasma cells and the BME can render myeloma cells resistant to current regimens of pharmacologic therapy, a mechanism coined, “cell adhesion-mediated drug resistance” (CAM-DR) (58)."

sparser
"On the contrary, the W1PR2 cell line revealed an increased level of extracellular COL3A1 after piperine treatment that may strengthen the CAM-DR mechanism and lower PAC sensitivity."

sparser
"Indeed, in the W1PR2 cell line, we observed a minimal synergistic effect of piperine on PAC resistance that may be explained by the protective effect of extracellular COL3A1 in the way of CAM-DR."

sparser
"Cell adhesion can mediate p27 kip1 elevation and it is associated with cell cycle arrest. xref , xref , xref Our study, for the first time, demonstrated that the negative correlation between VRK1 and p27 kip1 expression might be the reason for cell cycle arrest and CAM-DR in MM cells."

sparser
"The possible roles of collagens in drug resistance can be related to direct drug binding [ xref ], physical drug diffusion blocking [ xref , xref ], and induction of CAM-DR [ xref , xref ] and were discussed in more details previously [ xref , xref ]."

sparser
"Finally, next to the above described role of EZH2 in IMiD and PI resistance, it should be mentioned that Kikuchi et al. also described a correlation between phosphorylation-mediated inactivation of EZH2 and cell adhesion-mediated drug resistance (CAM-DR) against doxorubicin and the alkylating agent 4-OHCY in MM."

sparser
"This protects them from killing by cytotoxic drugs, so called cell adhesion-mediated drug resistance (CAM-DR), but also from killing by cytotoxic T−cells (CAM-immune resistance/CAM-IR) by upregulating several anti-apoptotic proteins after binding to stromal cells [ xref ]."

sparser
"Stromal cells utilize two mechanisms to induce drug resistance, including soluble factor-mediated drug resistance (SM-DR) and cell adhesion-mediated drug resistance (CAM-DR) [ xref ]."
| PMC

sparser
"Altogether, we can draw a preliminary conclusion that WCF combined with DDP reverses the CAM-DR, perhaps by inhibiting the expression of Integrin β1 and its ligand proteins."

sparser
"Surface molecule overexpression and CAM-DR have been addressed in many subtypes of leukemia, including B- and T-acute lymphoblastic leukemia (B- and T-ALL) and acute myeloid leukemia (AML)."

sparser
"Adhesion of leukemia cells to BM stromal cells may lead to cell adhesion-mediated drug resistance (CAM-DR) mediating intracellular signaling changes that support survival of leukemia cells."

sparser
"Given that the adhesion of MM cells to BMSC via VLA-4- VCAM-1 interaction confers CAM-DR in MM cells xref , xref , xref and osteoclastogenesis, xref these results suggested the therapeutic impact of TAK1 inhibition on CAM-DR as well as osteoclastogenesis induced by the MM-bone marrow interaction."

sparser
"This appears indicative for the ITGB1/COL1 axis triggering the CAM-DR process ( xref a)."

sparser
"WNT and Activation of Cell Adhesion-Mediated Drug Resistance (CAM-DR): CD44."

sparser
"CAM-DR is one mechanism through which leukemia cells obtain chemoresistance, and resistant clones will result in the recurrence of the disease."

sparser
"CAM-DR may be strong in minimal residual myeloma cells compared to newly diagnosed myeloma cells because of the rich presence of adhesion molecules on the minimal residual myeloma cells [ xref ]."

sparser
"Based on the ability of AMG9810 to suppress CXCR4 expression and activation on MM cells and given the role of CXCR4 in contact-dependent drug resistance (CAM-DR) of MM cells, we evaluated the effect of TRPV1 inhibition on stroma-mediated protection."

sparser
"Cell adhesion-mediated drug resistance (CAM-DR) is a process involved in chemoresistance and operates in B-ALL ( xref ) and in the response of MM cells to the proteasome inhibitor bortezomib (BTZ) ( xref – xref )."

sparser
"CAM-DR has attracted the primary attention in the treatment of multiple myeloma, but since then has also been accepted for its relevance in various solid tumors [ xref , xref ]."

sparser
"The gene set enrichments showed that sustained PI monotherapy was involved in inflammatory response pathways, which correspond to SFM-DR, whereas the gene sets involved in CAM-DR were enriched in both combination and intermittent therapy groups (Fig.  xref )."

sparser
"Therefore, therapeutic interference with CAM-DR appears promising to antagonize resistance as an early onset mechanism, relevant for different other types of resistance formation."

sparser
"By promoting a better survival of blasts, the stroma-induced SP functionality we identified in blasts could represent a new mechanism of CAM-DR."

sparser
"Concerning the mechanistic background of CAM-DR, although the binding to COL1 induces a comparable loss in sensitivity in both W1 and W1CR cells by doubling the EC 50 values, the underlying mechanisms appear to be diverse, following different routes in both cells."

sparser
"Hence, BTK bound directly with CXCR4 and prevented its ubiquitination-induced degradation, leading to CAM-DR maintenance."

sparser
"Furthermore, CAM-DR emerges as an independent process adding to the resistance phenomena already developed in ovarian cancer cells, which has not been shown before."

sparser
"It is accepted that CAM-DR contributes drug resistance to melphalan, vincristine, doxorubicin, mitoxantrone, and bortezomib [ xref , xref ]."

sparser
"This opens the view to other potential COL1 binding proteins contributing to CAM-DR."

sparser
"In addition, down-regulation of VRK1 expression resulted in induced CAM-DR phenotype, which was accomplished by enhancing the ability of cell adhesion."

sparser
"Cadherins, selectins, and integrins are known cell adhesion molecules that are involved in CAM-DR in leukemia ( xref )."

sparser
"The ITGB1 knockdown confirms that CAM-DR follows a COL1/ITGB1 signaling axis in W1 cells; thus, a blockade of ILK re-sensitized W1 cells on COL1 for cisplatin."

sparser
"CAM-DR plays an important role in drug resistance through the adhesion between Integrin β1 and ECM."

sparser
"Their aberrant expression and association in CAM-DR in different types of leukemia have been studied."

sparser
"These biological processes and pathways correspond to soluble factor-mediated drug resistance (SFM-DR) and cell adhesion-mediated drug resistance (CAM-DR), xref respectively."

sparser
"In addition, bortezomib was found to overcome CAM-DR in BL cells by inhibiting NF-κB. Thus, bortezomib may have potential clinical applications in the treatment of CD49d- and CD49e-mediated CAM-DR in BL patients."

sparser
"The bone marrow environment has been shown to promote CAM-DR in ALL ( xref )."

sparser
"Thus, the limitation of TGFBI secretion by piperine can inhibit integrin signaling, which is the primary signaling in CAM-DR, and it eventually leads to higher TOP sensitivity [ xref ]. xref summarizes the main mechanisms of piperine action on drug-resistant cells in our model."

sparser
"USP14 reportedly contributes to CAM-DR by upregulating the anti-apoptotic protein Bcl-xl and Wnt 3 signaling pathways."

sparser
"Other integrin, including β7-integrin and VLA-5 (α5β1), also plays a role in CAM-DR of MM cells [ xref ]."

sparser
"SFM-DR is primarily mediated by the induction of gene transcription, whereas CAM-DR is mediated largely, but not entirely, by non-transcriptional mechanisms including the degradation of activators of apoptosis [ xref ], subcellular redistribution [ xref ], and increased stability of suppressors of apoptosis and cell cycle regulators [ xref ]."

sparser
"The binding of MM cells to fibronectin upregulates p27 and induces nuclear factor κB (NFκB) activation in MM cells [ xref ], which confer cell adhesion-mediated drug resistance (CAM-DR) to conventional chemotherapy [ xref ]."

sparser
"CDC5L interference inhibited the CAM-DR in MM cells to alleviate the promotion effects of ANXA7 overexpression on CAM-DR to make MM cells become more susceptible to bortezomib."

sparser
"Our data suggest that HSPA12B may play a functional role in CAM-DR and is thus a potential novel target for NHL treatment."

sparser
"Adhesion of acute lymphoblastic leukemia (ALL) cells to bone marrow stroma cells triggers intracellular signals regulating cell-adhesion-mediated drug resistance (CAM-DR) [ xref , xref ]."

sparser
"Binding to ECM components, also referred to as cell adhesion-mediated drug resistance (CAM-DR), appears as a functional onset to escape cytotoxic stress rapidly at a non-genetic basis and, thus, as a premise for subsequent genetic adaptations."

sparser
"However, the molecular mechanism underlying CAM-DR in BL has not been identified yet."

sparser
"BTK plays a role in CAM-DR through the regulation of CXCR4 degradation in MM cells and suggests that targeting therapy for the BTK/CXCR4 interaction may be effective for reversing CAM-DR."

sparser
"ANXA7 overexpression increases the cell adhesion-mediated drug resistance (CAM-DR), which was inhibited by ANXA7 interference."

sparser
"It strongly indicates that CAM-DR is associated with post-transcriptional mechanisms while the acquired drug resistance is associated with specific transcriptomes’ change [ xref ]."

sparser
"Cell-adhesion mediated drug resistance (CAM-DR) to melphalan is induced in MM cell lines and in patient primary cells through adhesion to fibronectin or bone marrow stromal cells (BMSCs), which is mediated by very late antigen-4 (VLA4) integrin (α4β1) and VLA-5 (α5β1) [ xref ]."

sparser
"Thus, induction of β1-integrin, which causes VLA-4-mediated CAM-DR in MM, is characterized by G1 cell cycle arrest accompanied by an increase of expression in CDK inhibitors, p21 Cip1 /Waf1 and p27 Kip1 [ xref ], and a decrease in Bim (an apoptotic BCL-2 family) [ xref ] and Cyclin A and Cyclin E activity [ xref ]."

sparser
"Furthermore, CAM-DR can also augment signaling pathways that cause increased expression of soluble factors in conferring tumor cell drug resistance."

sparser
"Numerous studies have demonstrated that cell-adhesion mediated drug resistance (CAM-DR) is based on a number of mechanisms."

sparser
"Multiple myeloma (MM) is a hematological neoplasia in which the BMN’s role in disease progression via elevated proliferation, migration and CAM-DR has been extensively reported [ xref ]."

sparser
"In vitro studies show that contact between leukemia and stromal cells promotes cell adhesion-mediated drug resistance (CAM-DR) [ xref , xref ], which prevents apoptosis of ALL cells [ xref , xref , xref ]."

sparser
"In contrast, CAM-DR adds to cisplatin resistance in W1CR cells independent of ITGB1."

sparser
"Introduction of miR-202 mimics into BMSCs inhibits the NF-κB signaling pathway and reverses CAM-DR [ xref ]."

sparser
"Several articles have been published supporting a role for CD44 in CAM-DR."

sparser
"On the other hand, the ECM model establishes the role of ECM-producing cells as responsible for development of drug resistance and its induction in surrounding cells via CAM-DR mechanism [ xref , xref ]."

sparser
"In such structure another mechanism of drug resistance like limited drug diffusion or cell adhesion mediated drug resistance (CAM-DR) can be important [ xref ]."

sparser
"Cell adhesion mediated-drug resistance (CAM-DR) is an established mechanism used by MMC to survive chemotherapy and its markers are upregulated in residual disease."

sparser
"Here we elucidate whether CAM-DR occurs in ovarian cancer cells and contributes to still-existing cisplatin resistance."

sparser
"This highly dynamic adaptation of malignant tumor signaling argues for a multitarget-inhibition approach, which is shown here to successfully interrupt CAM-DR."

sparser
"However, the specific role of VLA-3 in CAM-DR in leukemia is still unclear."

sparser
"During treatment, leukemia cells interact with the bone marrow (BM) microenvironment and obtain a survival benefit, known as cell adhesion-mediated drug resistance (CAM-DR) ( xref )."

sparser
"In particular, adhesion between MM cells and bone marrow stromal cells mediated by adhesion molecules induces cell adhesion-mediated drug resistance (CAM-DR)."

sparser
"As a receptor of hyaluronic acid (HA), CD44 confers resistance to lenalidomide in myeloma cells as the factor that CD44/HA adhered to BMSCs more strongly in lenalidomide-resistant MM cells, suggesting CD44 and BMSC-mediated CAM-DR [ xref ]."

sparser
"Integrin β1 signaling plays an important role in CAM-DR and has been proposed as a potential target for NSCLC."

sparser
"This adhesion mediated drug resistance referred to as CAM-DR was not caused by reduced drug accumulation or upregulation of anti-apoptotic Bcl-2 family members [ xref , xref ]."

sparser
"These initial results of preclinical studies suggest inhibitors of Notch signaling as potential anti CAM-DR drugs and further studies are warranted."

sparser
"The lack of CAM-DR effect against BRZ, induced by the interaction with hyaluronic acid and collagen, has been confirmed."
| PMC

sparser
"Altogether, our results demonstrate that the stroma-induced SP functionality is a new mechanism of CAM-DR for AML blasts."

sparser
"Previous studies indicated that adhesion of hematologic malignancies cells to FN leads to a reversible cell cycle arrest, which in turn promotes CAM-DR. xref , xref Hence, it is necessary for us to elucidate the correlation between cell adhesion and the expression of VRK1."

sparser
"Interaction between VLA-4 and vascular cell adhesion molecule-1 (VCAM-1) binds between MM cells and BMSC, contributing to the survival of MM cells via activation of phosphoinositide 3-kinase (PI3K)/(protein kinase B) AKT pathway and CAM-DR [ xref ]."

sparser
"EM-DR is rapidly induced by signaling events that are initiated by factors present in the tumor microenvironment and can be subdivided into two categories: soluble factor-mediated drug resistance (SFM-DR), which is induced by cytokines, chemokines, and growth factors secreted by MSCs such as IL-6, IGF-1, IL-1, IL-17 and TNF-α; and cell adhesion-mediated drug resistance (CAM-DR), which is mediated by the adhesion of tumor cell integrins to MSCs or stromal fibroblasts or components of the ECM, such as fibronectin, laminin, hyaluronan and collagen IV [ xref , xref , xref , xref ]."

sparser
"The significant increase in W1CR resistance induced by COL1 points to the fact that CAM-DR is obviously an independent process contributing to the already existing cisplatin resistance of W1CR, but is not the basis for the “intrinsic” resistance."

sparser
"Recent studies have verified that the BM microenvironment which provides a niche that promotes MM cells survival must be considered when evaluating drug response. xref Specially, MM cells adhered to FN or stromal cells conferred a multidrug resistant phenotype, known as CAM-DR, owing to the cell cycle arrest. xref Therefore, a hypothesis was proposed that abnormal expression of cell cycle regulators might be conduced to CAM-DR, then we focused on identifying them as targets to overcome CAM-DR."

sparser
"So far, there is one study that has reported its relationship with head and neck cancer, indicating that ENO1 promotes transformation partly via chemokine CCL20 induction and can be regarded as a potential prognostic marker. xref Moreover, ENO1 participates in the process of lymphoma cell adhesion mediated drug resistance (CAM-DR), besides promoting tumor proliferation. xref ENO1 overexpression was also observed in pancreatic cancer, xref and ENO1 silencing could sensitize hypoxia-induced chemoresistance. xref Some Italian scholars used a genetic model of pancreatic carcinoma and observed the effects that vaccination with ENO1 DNA elicits."

sparser
"Overexpression of miR-21 suppresses its targets, such as phosphatase and tensin homolog (PTEN), PUMA, and RhoB, which promote MM viability and contribute to CAM-DR [ xref , xref ]."

sparser
"Cell adhesion-mediated drug resistance (CAM-DR), a form of chemotherapy resistance, has been reported to confer resistance to various chemotherapeutic agents."

sparser
"Kikuchi et al. demonstrated that pharmacological and genetic inhibition of the IGF1R-PI3K-AKT pathway reverses CAM-DR by promoting enhancer of zeste homolog 2 (EZH2) dephosphorylation and H3K27 hypermethylation both in vitro and in refractory murine MM models, suggesting an epigenetic mechanism underlying CAM-DR [ xref ]."

sparser
"In addition to increases in transporter genes, Fibronectin-1 was also massively augmented, which lead the authors to propose a cell adhesion mediated drug resistant (CAM-DR) phenotype, in which anchorage to the ECM appears essential for cell survival in the presence of antineoplasic drugs."

sparser
"In search of novel targets to sensitize breast cancer cells against the guideline-based drugs MX and CDDP, we focused on CAM-DR."

sparser
"At the same time, leukemia cells can aberrantly express CAM to facilitate surface molecule-mediated interaction with BM microenvironment, thereby inducing cell-adhesion mediated drug resistance (CAM-DR)."

sparser
"BMSC-derived CXCL12γ and HSPGs mediate CAM-DR."
| PMC

sparser
"MGr1-Ag can prompt CAM-DR through interaction with laminin while MGr1-Ag/37LRP, as a receptor for ECM components, may interact with phosphorylated FAK to activate downstream signaling pathways PI3K/AKT and MAPK/ERK."

sparser
"In contrast, a clear CAM-DR was observed for H929 cells treated with AUR alone or BTZ alone (+ 20.6% and +12.0% of viability, respectively)."

sparser
"Although the combination of ERK1/2 and EGFR blockade in breast cancer has been demonstrated before using MEK1/2-inhibitors [ xref , xref ], combination in the context of CAM-DR or COL1 dependency have not been described so far."

sparser
"Data of this study provide evidence for the role of CAM-DR in breast cancer cells to attenuate the sensitivity to the guideline based cytotoxic drugs MX and CDDP."

sparser
"Our study revealed that the therapeutic basis for SFM-DR as well as for CAM-DR is the dysregulation of epigenetic regulators in MM patients during treatment."

sparser
"To further evaluate the effects of prior drug exposure in the context of CAM-DR, patient stroma–MMC co-cultures were exposed to dexamethasone for 24h, washed to remove the free drug and non-adherent cells, then treated with V-ND or V-CP."

sparser
"KO cells also overexpressed N-cadherin, expressed by osteogenic precursors, and ICAM1, also implicated in adhesion and CAM-DR."

sparser
"For example, protecting cells from drug-induced cytotoxic damage in cancer cells with CAM-DR was achieved by enhancing the repair of DNA damage due to overexpression of histone methyltransferase multiple myeloma SET domain (MMSET) in multiple myeloma [ xref , xref ], or elevated expression of FANCF and RAD51C which are important DNA repair proteins [ xref , xref , xref , xref , xref , xref ]."

sparser
"Integrins, a family of heterodimeric adhesion molecules with ubiquitous cellular expression, represent the most important group of candidates to be involved in CAM-DR."

sparser
"Therefore, identifying the underlying mechanism of this survival promoting CAM-DR is critical to overcoming chemotherapeutic drug resistance."

sparser
"The changes in EC 50 values are not as high as in genetically resistant cell lines, based on the epigenetic nature of CAM-DR."

sparser
"Anti CD38 MoAbs have several anti-myeloma and microenvironment activities, such as complement-dependent cytotoxicity (CDC), ADCC, direct myeloma killing, enhancement of the immune system, inhibition of CAM-DR, and enhancement of bone remodeling as above."

sparser
"MM adhesion to hyaluronan also confers CAM-DR to MM cells [ xref ], and OPN has been shown to mediate multidrug resistance in other cancers by enhancing hyaluronate binding and may act similarly in MM [ xref ]."

sparser
"De novo resistance includes environment-mediated drug resistance, which is categorized as either cell adhesion-mediated drug resistance (CAM-DR) or soluble factor-mediated drug resistance (SFM-DR)."

sparser
"A recent study has also shown that CXCL12 is a relevant target to attenuate CAM-DR in MM [ xref ]."

sparser
"Consequently, ITGB1 activity has been shown to be dominant to confer CAM-DR to tumor cells of different origin upon binding to COL1 [ xref , xref ]."

sparser
"Interference with this pathway has been shown to alleviate CAM-DR phenomena in hematopoietic cells [ xref ]."

sparser
"Cadherins, Selectins, and Integrins in CAM-DR in Leukemia."

sparser
"Second, the TME might aid cancer cell survival and induce epithelial–mesenchymal transition (EMT) through the enhanced adhesion of cancer cells to the ECM, leading to therapeutic resistance, often described as cell adhesion-mediated drug resistance (CAM-DR) [ xref , xref , xref ]."

sparser
"Therefore, clarification of the molecular systems inherent in CAM-DR may facilitate identification of new therapeutic tactics to overcome this problem."
| PMC

sparser
"Since integrin binding activity does not only regulate a physical cell embedding into an ECM, but also activates specific signaling pathways, integrins appear as relevant candidates for mediating CAM-DR."

sparser
"Taken together, our data suggest a scenario in which CXCL12γ functions as a ‘niche chemokine’ that, in conjunction with HSPGs, plays a key role in controlling adhesion, BM retention, and CAM-DR of MM cells (Fig.  xref c)."
| PMC

sparser
"Both ectopic expression of miR-548m and knockdown of HDAC6 were able to disrupt the stroma-lymphoma adhesion and consequently induce cell apoptosis, suppress colony formation, sensitize B-lymphoma cells to the cytotoxic drug mitoxantrone, and abolishing the cell adhesion–mediated drug resistance acquisition (CAM-DR) [ xref ]."

sparser
"The resistance is believed to be selected during a treatment course, which contributes to acquired drug resistance by CAM-DR [ xref ]."

sparser
"Since expression of the majority of adhesion molecules including VLA-4 is regulated by NF-κB, inhibition of NF-κB may represent a novel strategy to overcome CAM-DR."

sparser
"Considering the extensive collagenous areas of e.g., collagen type 1 (COL1) surrounding the lobules forming the connective tissue in the mammary gland, breast cancer appears highly probable to undergo CAM-DR and to make use of this mechanism."

sparser
"Fn could decrease the apoptosis-inducing effect of TMZ and led to the CAM-DR in glioma cells."

sparser
"The integrin VLA4 (α 4 β 1 ) is a key mediator of CAM-DR and its expression affects drug sensitivity of MMC."

sparser
"Our previous studies have shown that cell adhesion-mediated drug resistance (CAM-DR) plays a crucial role in relapsed and refractory B-ALL ( xref , xref )."

sparser
"This type of drug resistance, named “cell adhesion-mediated drug resistance” (CAM-DR), is regarded as the most important mechanism able to cause the escape of MM cells from therapeutic effects [ xref , xref ]."
| PMC

sparser
"In this way, the implication of two biomolecules, hyaluronic acid and collagen, have been proven on mPCs proliferation and CAM-DR effect towards DEX and BRZ."
| PMC

sparser
"The PI3K/AKT pathway is a central hub in drug resistance of leukemia, particularly in CAM-DR, involving several downstream signaling pathways that support survival and proliferation of leukemia cells."

sparser
"Notably, in the MCF-7-β1-integrin knockdown cells, inhibition of MEK, and even more ERK and CREB is efficient to overcome COL1 induced CAM-DR and foster cell sensitization."

sparser
"Thus, EZH2 is a target of treatment for the apoptosis of myeloma cells and release of CAM-DR [ xref , xref ]."

sparser
"All in all, these findings illustrate the potential of a therapeutic interference with intracellular signaling pathways, differing in the various tumor entities, to disrupt the processes of CAM-DR and therefore deprive the cells of the suitable conditions to generate genetically based resistance mechanisms at an early onset point."

sparser
"Tumor cell binding to microenvironment components such as collagen type 1 (COL1) attenuates the sensitivity to cytotoxic drugs like cisplatin (CDDP) or mitoxantrone (MX), referred to as cell adhesion mediated drug resistance (CAM-DR)."

sparser
"MM cell adhesion to BMSC through the interaction between VLA-4 and its corresponding ligand, VCAM-1, is among the predominant mechanisms for cell adhesionmediated drug resistance (CAM-DR) in MM, xref , xref while enhancing the production of IL-6 30 and RANKL, an critical osteoclastogenic factor in MM. xref In addition to TAK1 activation in MM cells, TAK1 was found to be phosphorylated along with PIM2 upregulation in BMSC, when cocultured with MM cells ( xref )."

sparser
"CD44 is an adhesion molecule found on the MM cell surface that mediates binding to BMSCs, which induces IL-6 secretion and cell adhesion mediated-drug resistance (CAM-DR) [ xref ]."

sparser
"The CAM-mediated interaction of leukemia cells with the surrounding microenvironment contributes to drug resistance, which is called cell adhesion-mediated drug resistance (CAM-DR)."

sparser
"In case of De Novo drug resistance transiently acquired by signaling cascade in tumor microenvironment by cell-adhesion mediated drug resistance (CAM-DR) or soluble factor-mediated drug resistance (SFM-DR) ( xref )."

sparser
"On the other hand, CAM-DR suppresses drug-induced apoptosis through other well-characterized mediators of drug resistance such as P-glycoprotein, fibronectin, laminin, and collagen IV [ xref ]."

sparser
"These data clearly confirm that the CAM-DR follows other pathways in the W1CR cells than the ITGB1 route relevant for W1 wild type cells."

sparser
"PTPRK can influence CAM-DR by dephosphorization of the AKT and MAPK pathways [ xref ]."

sparser
"Concluding, we provide evidence for importance of CAM-DR in breast cancer cells and identify intracellular signaling pathways as targets to sensitize cells for cytotoxicity treatment regimes."

sparser
"CAM-DR, a form of chemoresistance, is mediated by the adhesion of tumor cells to the extracellular matrix (ECM) which enhances tumorigenicity and suppresses chemotherapy‐induced apoptosis to confer resistance to chemotherapeutic agents ( xref )."

sparser
"Conversely, the amount and the structure of “finger-like” collagen, which can also result in cell adhesion mediated drug resistance (CAM-DR), was destroyed after GLPM/Tel treatment."

sparser
"Furthermore, Wang et al. recently demonstrated that BTK induces CAM-DR through CXCR4 regulation degradation in MM [ xref ], promoting BTK expression induced MM cell adherence to the extracellular matrix and stromal cells in vitro and in vivo and increased drug resistance to bortezomib and doxorubicin in MM cells."

sparser
"DARA releases CAM-DR by inhibiting adhesion to BMSCs by internalizing CD38 in myeloma cells [ xref ]."

sparser
"CAM-DR has initially been described as a rapid, nongenetic adaptation of leukemia cells to cytostatics for an increased survival of treatment, associated with the phenomenon of minimal residual disease [ xref , xref ]."

sparser
"One of the prominent features of cell adhesion-mediated signaling in MM pathogenesis is cell-adhesion mediated drug resistance (CAM-DR)."

sparser
"EMDR can be separated in two groups: EMDR due to soluble factors which is called Soluble Factor-Mediated Drug Resistance (SFM-DR), and EMDR due to adhesion process between the tumor cell receptors and extracellular matrix (ECM) proteins which is called Cell Adhesion-Mediated Drug Resistance (CAM-DR)."

sparser
"These findings support the post-transcriptional mechanisms of CAM-DR, all of which is accomplished by the modulation of ubiquitin-dependent degradation mechanisms."

sparser
"ITGB7 is necessary for myeloma cell survival and CAM-DR, and has been shown to be constitutively active in myeloma cells ( xref , xref )."

sparser
"In vitro studies show that contact between leukemia and stromal cells and other non-cellular components of the BM promotes cell adhesion-mediated drug resistance (CAM-DR) ( xref ; xref ), which prevents apoptosis of ALL cells ( xref ; xref ; xref )."

sparser
"The transcriptional regulation of Ephrin receptors, whose expression is frequently augmented in tumors, might provide a further mechanism of CAM-DR promotion through Teneurins."

sparser
"However, CD49a, CD49b, CD11a, CD29, CD18, and CD61 were not found to be associated with CAM-DR in BL cells."

sparser
"Therefore, even though specific ligands are preferentially used in different cells, this does not mean that other molecules are less crucial in conferring CAM-DR."

sparser
"In addition, CAM-DR also elicits resistance through blocking a specific element of the caspase-mediated apoptotic pathway."

sparser
"The ECM model of drug resistance development postulates that small populations of tumor cells express ECM molecules at high levels and only these cells survive chemotherapy because of CAM-DR [ xref , xref , xref , xref , xref , xref , xref , xref ]."

sparser
"In these clinical trials, GMI-1271 will be administered in combination with existing chemotherapies, which highlights how targeting both the microenvironment and leukemia cells may be necessary in order to ameliorate CAM-DR."

sparser
"However, due to the complexity of the bone marrow microenvironment and the diversity of the niche delineating diagnostic biomarkers of response signatures for targets associated with SM-DR, CAM-DR and EM-DR will be required to guide combination strategies with standard of care agents to improve individualized patient outcomes."

sparser
"The mechanisms of resistance in cancers due to bone marrow microenvironment effects are best explained majorly by two forms of environment factors, which are soluble factor-mediated drug resistance (SFM-DR) and cell-adhesion-mediated drug resistance (CAM-DR) [ xref , xref ] and in the MM situation."

sparser
"At present, several integrins have been proposed as likely contributors to CAM-DR in ALL and different routes of dissemination from BM to the CNS have been suggested ( xref , xref )."

sparser
"Furthermore, VRK1 could reverse cell adhesion mediated drug resistance (CAM-DR) by down-regulating the ability of cell adhesion."

sparser
"Moreover, suppression of the miR-30a-5p or upregulation of the BCL2L11 promoted apoptosis of the myeloma cells independent of the BMSCs, thus suggesting clinical significance of miR-30a-5p inhibitor and PLBCL2L11 plasmid in CAM-DR."

sparser
"ANXA7 was also demonstrated to be combined with CDC5L. Therefore, ANXA7 interference could promote cell cycle arrest in G2/M phase through CDC5L to inhibit proliferation of MM cells and reduce CAM-DR."

sparser
"This type of acquired resistance can be divided into two categories: soluble factor-mediated drug resistance (SFM-DR) and cell adhesion mediated drug resistance (CAM-DR) ( xref f)."

sparser
"Toward this goal, we identified trimethylation of histone H3 at lysine-27 (H3K27me3) as a critical histone modification associated with CAM-DR."

sparser
"Taken together, our results confirm that the combination of WCF with DDP could reverse the lung cancer CAM-DR through the Integrin β1 signaling pathway."

sparser
"This study aims to investigate the effect and mechanism of WCF combined with DDP in reversing CAM-DR."

sparser
"BOR enhances the activity of IMiDs by releasing CAM-DR and elevating IKZF1 expression."

sparser
"CAM-DR and SFM-DR are therapeutic targets to overcome drug resistance and to suppress the proliferation and survival of MM cells via the inhibition of signaling pathways."

sparser
"MSCs also contribute to drug resistance through cell-adhesion-mediated drug resistance (CAM-DR) [ xref , xref ], in which the Wnt signaling pathway is involved [ xref ]."

sparser
"This biological process is associated with a multidrug resistant phenotype, “cell adhesion-mediated drug resistance,” or CAM-DR [ xref ]."

sparser
"However, in the meantime, CAM-DR has been accepted as a phenomenon of de novo resistance with relevance for different solid tumor cells [ xref ], displaying a prerequisite for the acquisition of genetic drug resistance mechanisms."

sparser
"CDC5L interference inhibits the CAM-DR promotion effect of ANXA7."

sparser
"Inhibition of EZH is known to inactivate CAM-DR in vitro [ xref ]."

sparser
"Although on basis of these and similar findings in other tumor entities [ xref ], DDR1 emerges as a promising novel target to interfere with tumorigenicity, an explicit involvement of DDR1 in the process of CAM-DR is experimentally still lacking."

sparser
"As shown by the structure, the protein has an ability to interact with ECM, which can be important from a CAM-DR point of view."

sparser
"Background: Tumor cell binding to the microenvironment is regarded as the onset of therapeutic resistance, referred to as cell adhesion mediated drug resistance (CAM-DR)."

sparser
"Herein, we develop an ECM deprivation system (EDS) based on FN targeting self-assembly peptide for constructing nanofibers in the ECM of renal cell carcinoma (RCC), which contributes to (i) targeting and recognizing FN to form nanofibers for long-term retention in ECM, (ii) reversing anoikis resistance via arresting the FN signaling pathway, and (iii) serving as a drug-loading platform for sensitizing chemotherapy by ameliorating CAM-DR."

sparser
"Thus, CXCL12γ and HSPG on the cell surface of BMSCs promote MM cell adhesion to these BMSCs and thereby play an important role in CAM-DR."
| PMC

sparser
"While we found alterations in other metabolism-associated genes (e.g. PKM2, CS, IDH1, ACO2, FH, MDH2, or HK1)), we focused on examining the functional significance of ENO1 in the present study since: (1) a significant induction of ENO1 was noted during pDC-MM interactions versus other molecules; (2) ENO1 is essential for maintaining tumor cell metabolism and represents a potential therapeutic target in cancer [ xref – xref ]; (3) ENO1 promotes tumor cell proliferation and cell adhesion-mediated drug-resistance (CAM-DR) [ xref ] characteristic of MM; and (4) ENO1 functions as an immunoregulatory molecule both in T-regulatory cell differentiation and dendritic cell function [ xref , xref ]."

sparser
"The apoptosis-protective adhesion to stromal cells, termed cell adhesion-mediated drug resistance (CAM-DR), is another underlying mechanism of R-CHOP resistance in DLBCL.[ xref ]CAM-DR was revealed to correlate with rituximab resistance through ADAM metalloproteinase domain 12 ( ADAM-12 ) upregulation and phosphatidylinositol 3-kinase ( PI3K ) -Akt signaling modulation.[ xref ]However, as per findings reported by Lenz et al ,[ xref ]genetically identified non-malignant signatures of stromal-1 (fibrosis and myeloid infiltration) and stromal-2 (vessel formation) in pretreatment biopsies were found to be prognostically favorable and unfavorable for patients with DLBCL who received R-CHOP, respectively."

sparser
"Type I collagen plays an important role in tissues scaffolding but is also important in CAM-DR ( xref )."

sparser
"The adhesion molecules, such as very late angine-4 (VLA-4) plays an important role for CAM-DR [ xref ]."

sparser
"CAM-DR, on the other hand, is caused by direct cell-cell interactions ( xref ) [ xref ]."
| PMC

sparser
"In “Cell Adhesion Drug Resistance” (CAM-DR), signaling through adhesion molecules, engaged with the bone matrix and stromal cells ( xref ), protects MMC from chemotherapy ( xref , xref )."

sparser
"To figure out whether CAM-DR is an additional independent process or an integrative part of an already existing cisplatin resistance, we also apply a cisplatin-resistant subtype of W1 cells (W1CR)."

sparser
"Integrin families, such as Very Late Antigen-4 (VLA-4), Syndecan-1 (CD138, SDC1), CD44, Vascular Cell Adhesion Molecule-1 (VCAM-1), Lymphocyte Function-Associated Antigen-1 (LFA-1), Mucin-1 antigen (MUC-1), and Intercellular Adhesion Molecule-1 (ICAM-1), have been shown to associate with CAM-DR [ xref , xref ]."

sparser
"This sort of drug resistance, called “cell adhesion-mediated drug resistance” (CAM-DR), is considered one of the most relevant systems able to provoke the escape of MM cells from therapeutic actions [ xref , xref ]."
| PMC

sparser
"Although a recent study reported on an inverse relation of DDR1 expression and cisplatin sensitivity in ovarian cancer [ xref ], a potential role of DDR1 in CAM-DR of W1CR cells remains a matter of further investigations."

sparser
"In this regimen, THAL enhances the sensitivity of BOR and cytotoxic agents by improving hypoxia, and BOR, in turn, increases the sensitivity of doxorubicin and etoposide, whose activities are dependent on the cell cycle, through the release of CAM-DR."

sparser
"Thus, the re-expression of PTPRK after piperine treatment can result in decreased CAM-DR."

sparser
"Here we provide evidence for a direct link between ITGB1-mediated matrix binding properties and CAM-DR in W1 and W1CR cells, resulting in significantly attenuated cisplatin sensitivity."

sparser
"Here, we describe the discovery of these drug resistance mechanisms and the identification of promising therapeutic agents primarily targeting CAM-DR, mitochondrial transfer, and TNTs."

sparser
"Adhesion of MM cells to BMSC and fibronectin upregulates heat shock protein-70 (HSP-70), which confers CAM-DR; blocking HSP-70 results in an increase of melphalan-induced apoptosis and reverses the CAM-DR [ xref ]."

sparser
"Thus, integrin-mediated chemoresistance is perceived as a form of adhesion-mediated drug resistance (CAM-DR) ( xref )."

sparser
"Overexpression of this protein was observed in lenalidomide-resistant human multiple myeloma cell lines (HMCLs), and in correlation with that, increased adhesion to bone marrow (BM) stromal cells was detected, indicative of CAM-DR."

sparser
"In this study, we investigated the mechanism of CAM-DR induced by Fibronectin (Fn)."

sparser
"Strengthening our comprehension of miRNA production and activity in the MM cell−BM relationship will help us to identify novel drug targets to overwhelm CAM-DR [ xref , xref ]."
| PMC

sparser
"Intracellular signaling initiated by binding to the ECM seems to be fundamental for cell adhesion-mediated drug resistance (CAM-DR) [ xref , xref ]."
| PMC

sparser
"One of the resistance phenomena involved in MM is the cell adhesion mediated drug resistance (CAM-DR) [ xref , xref ]."
| PMC

sparser
"Most research targeting CAM-DR has focused largely on integrins [ xref , xref , xref , xref , xref , xref , xref , xref , xref , xref , xref , xref , xref , xref , xref , xref , xref , xref , xref , xref , xref , xref , xref , xref , xref ] (see xref )."

sparser
"Different ECM proteins, including laminin and fibronectin, are associated with CAM-DR in different cancer types [ xref ], including pancreatic cancer [ xref ]."

sparser
"Consequently, FAK and PI3K appear as promising targets in MCF-7 cells to interfere with CAM-DR and suggest a proof of concept experiment by a β1-integrin knockdown."

sparser
"The integrin VLA4 (a 4 b 1 ) is a key mediator of CAM-DR and its expression affects drug sensitivity of MMC."

sparser
"It has been previously reported that adhesion of myeloma cells to fibronectin (FN) via beta1 integrin is associated with CAM-DR, which may induce perturbation in cell cycle progression and protect cells from apoptosis via increasing p27 kip1 protein expression. xref Similar phenomenon also appears in lymphomas cells. xref In conclusion, these researches suggest that p27 kip1 can induce a cell cycle arrest through BM ECM and plays an important role in cell adhesion mediated regulation of cell cycle progression."

sparser
"Treatment for Interaction with CAM-DR and SFM-DR."

sparser
"Integrin β1 is almost ubiquitously expressed in cancer cells, which closely related to CAM-DR."

sparser
"The phosphorylation-mediated enhancer of zeste homolog 2 (EZH2) inactivation and subsequent decreases in H3K27me3 levels are related to CAM-DR in MM cells [ xref ]."

sparser
"Environmental mediated-drug resistance (EM-DR) contains cell adhesion mediated drug resistance (CAM-DR) and soluble factor mediated drug resistance (SM-DR) that contributes to de-novo drug resistance."

sparser
"1S cells to fibronectin could increase miRNA-182 production and reduce programmed cell death 4 (PDCD4), which is essential for CAM-DR."
| PMC

sparser
"Aptamer NOX-A12 had anti-myeloma CAM-DR activity ( xref )."

sparser
"Future studies will define the dependency of TRPC1 for survival in the bone-marrow microenvironment and whether this signaling pathway is required for growth, cell adhesion-mediated drug resistance (CAM-DR), or soluble mediate drug resistance (SM-DR)."

sparser
"It was previously demonstrated that the adhesion molecule integrin α4, referred to hereafter as α4, mediates the cell adhesion-mediated drug resistance (CAM-DR) of B-cell ALL by binding to vascular cell adhesion molecule-1 (VCAM-1) on bone marrow stroma."

sparser
"Although several studies illustrate a link between integrins and increased malignancy or resistance of ovarian cancer cells, a generalization of CAM-DR mediated mechanisms remain open."

sparser
"Binding of VLA-4 to fibronectin of the ECM induces activation of nuclear factor κB (NFκB) leading to cell adhesion-mediated drug resistance (CAM-DR) and pro-survival signaling ( xref )."

sparser
"Thus, heparin, heparan sulphate, chondroitin sulphate, or other collagens hypothesized to be involved in CAM-DR could be incorporated into the 3D environment with the procedures discussed here."
| PMC

sparser
"CAM-DR is induced in fibroblasts derived from MM patients, but not in healthy individuals [ xref , xref ]."

sparser
"Cell adhesion mediated-drug resistance (CAM-DR) is one of main reasons for. the limitation to chemotherapy, but the underlying mechanism remains unclear in glioma."

sparser
"Despite original responses to chemotherapy, MM patients finally develop drug resistance and become unresponsive to a wide spectrum of antineoplastic agents, a phenomenon called multidrug resistance (MDR). xref Accumulating evidence reveals that the bone marrow (BM) microenvironment which consists of hematopoietic cells, stromal cells, and extracellular matrix (ECM) confers resistance to chemotherapy. xref xref – xref Previous researches indicated that the direct adhesive interactions of myeloma cells with BM stromal cells and ECM components could transduce into the anti-apoptotic and cell cycle arrest signals and ultimately lead to MDR. xref – xref This protection phenomenon is termed as ‘cell adhesion mediated drug resistance’ (CAM-DR)."

sparser
"IGF-1R and PI3K/Akt inhibitors reversed this CAM-DR by blocking the IGF-1 mediated EZH2 phosphorylation ( xref )."

sparser
"As another more complex TME model, we tested the response of H929 and L363 BTZ-sensitive cells cultured on a layer of HS-5 bone marrow mesenchymal cells, mimicking the bone marrow environment and also allowing CAM-DR [ xref ]."

sparser
"Applying proteome profiler arrays, mapping the status of human kinases in both cell lines treated with MX and COL1, we investigated different β1-integrin related signaling molecules to explain underlying mechanisms of CAM-DR."

sparser
"Overexpression of CCT8 could promote the proliferation, accelerate the G1/S transition and reverse cell adhesion-mediated drug resistance (CAM-DR) phenotype in B-cell non-Hodgkin’s lymphoma ( xref )."

sparser
"However, the expression of ECM components and CAM-DR seems not to be limited to cancer tissue."

sparser
"Moreover, another study reported that CAM-DR is associated with activation of canonical NF-κB (p65–p50) in MM cells."

sparser
"Despite significant progress in the treatment of myeloma, multiple myeloma (MM) remains an incurable hematological malignancy due to cell adhesion-mediated drug resistance (CAM-DR) phenotype."

sparser
"VRK1 is regulated in cell cycle and its impact is mediated by the contribution to the coordination of several processes required for cell division. xref However, the role of VRK1 in MM, especially in CAM-DR, has never been reported."

sparser
"This study aimed to investigate the expression of HSPA12B and its role in cell adhesion mediated drug resistance (CAM-DR) of non-Hodgkin's lymphoma (NHL)."

sparser
"Studies have shown that USP14 is significantly overexpressed in CAM-DR models and downregulated in apoptotic models of MM."

sparser
"This phenomenon, called cell adhesion-mediated drug resistance (CAM-DR), has been demonstrated in many subsets of leukemia including B- and T-acute lymphoblastic leukemia (B- and T-ALL) and acute myeloid leukemia (AML)."

sparser
"Integrin β1 appears as a relevant candidate for mediating CAM-DR ( xref ; xref )."

sparser
"Together, these findings indicated that NRF2 could inhibit both the secretion of IL-6 and the expression of adhesion molecules in BMSCs; thus, reducing SFM-DR and CAM-DR ( xref )."

sparser
"The epigenetic mechanism is associated with CAM-DR as well."

sparser
"Interestingly, it has been observed in multiple studies that targeting NFκB signalling pathways when treating MM, reduces drug resistance to PIs xref , suggesting that the significantly increased abundance of Integrin β3 shown in this study may be leading to increased levels of NFκB signalling, causing CAM-DR to three of the five drugs."
| PMC

sparser
"Suppression of integrin β7 decreases adhesion to fibronectin and E-cadherin and inhibits CAM-DR to bortezomib or melphalan in MM cells [ xref ]."

sparser
"The attachment of tumor cells to the ECM may trigger cell adhesion-mediated drug resistance (CAM-DR)."

sparser
"Cell adhesion molecules that mediate the adhesion of MM cells to stroma cells play a critical role in cell adhesion-mediated drug resistance (CAM-DR) [ xref ]."

sparser
"Conclusions: CAM-DR appears relevant for ovarian cancer cells, adding to existing genetic resistance and thus emerges as a target for sensitization strategies."

sparser
"These data demonstrated the close cross-talk between SFM-DR and CAM-DR in the complex bone marrow microenvironment to the resistance of MM."

sparser
"Elucidation of the mechanisms underlying cell adhesion-mediated drug resistance (CAM-DR) may prolong remission and ultimately improve the survival of MM patients."

sparser
"However, daratumumab may also internalize CD38 in MM cells to inhibit adhesion to BMSCs and overcome CAM drug resistance (CAM-DR)[ xref ]."

sparser
"As discussed in this section, integrin blockades have been shown to increase chemosensitivity of leukemia cells and provide support for further studies of integrins as a viable target to abolish CAM-DR in leukemia."

sparser
"MiR-138 promoted CAM-DR phenotype through cell adhesion-mediated SGTA down-regulation and cell cycle arrest."

sparser
"There is increasing evidence that selectins play an important role in the progression of different types of cancer, in particular the interaction of tumor cells with the endothelium that is needed for extravasation and the formation of new metastatic lesions [ xref , xref ] Selectins are molecules expressed on the cell surface of endothelial cells that have been shown to promote the first interaction between an extravasating cell and the blood-vessel wall [ xref ], and have been implicated in CAM-DR [ xref , xref , xref , xref ]."

sparser
"This study gives a link to CAM-DR in the clinical setting of ovarian cancer."

sparser
"Adhesion of acute lymphoblastic leukemia (ALL) cells to bone marrow stroma cells triggers intracellular signals regulating cell-adhesion-mediated drug resistance (CAM-DR)."

sparser
"Simvastatin as an inhibitor of CAM-DR in patients with refractory multiple myeloma was tested in Phase II clinical trials by Ludwig-Maximilian University of Munich."

sparser
"We hypothesized that the reversal of drug resistance is related to the decline of ECM proteins or participators of CAM-DR."

sparser
"Nevertheless, the molecular mechanisms of CAM-DR remain elusive."

sparser
"The interaction of cancer cells with ECM activates the intracellular signaling leading to cell adhesion-mediated drug resistance (CAM-DR) [ xref , xref ]."

sparser
"CAM-DR induces a multidrug resistant phenotype as cell adhesion can protect tumors cells from multiple structurally and mechanistically diverse chemotoxic agents in MM [ xref , xref – xref ] and leukemia model systems [ xref – xref ]."

sparser
"Our observation of chemoresistance for SK-OV-3 ( xref and xref ) in RGD- and collagen I (GFOGER)-conjugated PeptiGels could also be due to the CAM-DR phenomenon, although further studies are needed to validate this."

sparser
"Several new drugs are developed to overcome de novo drug resistance, such as proteasome inhibitors and EZH2 inhibitors to overcome CAM-DR, and anti-IL-6 monoclonal antibodies and IGF-1R inhibitors to overcome SFM-DR, in a preclinical study, although several of those have not shown efficacy in clinical trials and thus are not available in clinical practice."

sparser
"Such a protective microenvironment has been reported to be implicated in the stemness and chemoresistance of leukemia blasts at the origin of the process of Environment Mediated-Drug Resistance (EM-DR), and specifically of Cell Adhesion Mediated-Drug Resistance (CAM-DR). xref , xref Quiescence, as well as protection against environmental and drug aggressions, are major characteristics of stem cells also characterized by the Side Population (SP) phenotype. xref We have previously shown that, whereas circulating HSPC from heathy donors (HD) do not exhibit a SP phenotype, this functionality can be induced after co-culture with MSC in a VLA4- and CD44-dependent manner. xref Interestingly, this MSC-induced SP population is enriched in HSC, as shown by its engraftment in immunodeficient mice. xref "

sparser
"Our previous studies have identified the integrin α4 and α6 as an adhesion molecule that plays a critical role in B-ALL through CAM-DR ( xref , xref )."

sparser
"Also, the Ephrin receptor-A4 (EPHA4) was required for CAM-DR in multiple myeloma (Ding et al., xref ), and Teneurins are known regulators of Ephrin receptor expression in structures of the visual system (Young et al., xref ; Glendining et al., xref )."

sparser
"Drug resistance mediated by the MM BM microenvironment can be caused either by soluble factors or by direct physical cell–cell interactions mediated by cell adhesion molecules, termed soluble factor-mediated drug resistance (SFM-DR) and cell adhesion-mediated drug resistance (CAM-DR), respectively [ xref , xref , xref ]."
| PMC

sparser
"Furthermore, ANXA7 overexpression promoted the CAM-DR in MM cells to make MM cells become more insusceptible to bortezomib while inhibited by ANXA7 interference."

sparser
"These data emphasize the upregulation of α4β1 expression and function as a key event during resistance to BTZ in MM, which might indirectly contribute to stabilize this resistance, as stronger MM cell attachment to BM stroma will regain CAM-DR and MM cell growth and survival."

sparser
"The PI3K-AKT pathway has been identified as one of the most significant pro-survival pathways in CAM-DR and leukemia cell-BM stromal cell contact has been shown to upregulate phosphorylated AKT in B-ALL ( xref )."

sparser
"Overexpression of USP14 in MM cells significantly enhances cell adhesion-mediated drug resistance (CAM-DR) through the upregulation of the Wnt signaling."

sparser
"Moreover, matrix remodeling by CAFs can form the chemoprotective niche and hence blocks the effective delivery of chemotherapeutic drugs to the cancer cells via cell adhesion-mediated drug resistance (CAM-DR), contributing its role in evading cancer cells to treatment (Meads et al. xref )."

sparser
"Considering the key role of CAM-DR as an early form of resistance formation, an insight into the underlying molecular pathways could provide novel targets for early pharmacological interference with resistance formation."

sparser
"Together, our data demonstrated the role of P65-miR-30a-5p-BCL2L11 loop in CAM-DR myeloma cells."

sparser
"Although CAM-DR has initially been described in multiple myeloma and other malignancies of hematopoietic origin [ xref ], which has been related to the minimal residual disease phenomenon [ xref ], some recent reports refer to CAM-DR in solid tumors, too."

sparser
"Similarly to VLA4, VLA5 (α 5 β 1 ) can bind fibronectin, and LFA-1 (α L β 2 ) is a known mediator of CAM-DR."

sparser
"Several studies described above have suggested that a TGF-beta signaling activation-related ECM of tumor cells can play a role in cell adhesion-mediated drug resistance (CAM-DR), such as resistance to platinum drugs ( xref )."

sparser
"However, the underlying mechanisms of CAM-DR are still not fully understood."

sparser
"In this study, we investigated the molecular mechanism responsible for CAM-DR in BL cells."

sparser
"A growing body of evidence indicates that cell-cell and cell-extracellular matrix (ECM) contacts can modulate drug resistance and the phenomenon is referred to as cell adhesion-mediated drug resistance (CAM-DR) [ xref , xref ]."

sparser
"Thus, cell adhesion mediated drug resistance (CAM-DR) appears as functional onset to escape cytotoxic stress for different tumor cell entities."

sparser
"The most important was to study the expression changes of HSPA12B in the adhesion model and the effect of overexpression of HSPA12B on CAM-DR."

sparser
"Therefore, identifying the underlying mechanism of survival and promotion of CAM-DR may be critical to target chemotherapeutic drug resistance in leukemia ( xref )."

sparser
"However, CDC5L interference increased cell apoptosis which reversed the CAM-DR promotion effect of ANXA7 on U266 cells ( xref )."

sparser
"Elucidating the mechanism of CAM-DR and developing the corresponding drugs are urgently required to improve outcomes."

sparser
"This paper will review the role of cadherins, selectins, and integrins in CAM-DR and the results of clinical trials targeting these molecules."

sparser
"Hence, VRK1 appeared to have specific effects on CAM-DR which was similar to apoptotic proteins."

sparser
"Extracellular matrix (ECM) is crucial in various biological functions during tumor progression, including induction of anoikis resistance and cell adhesion-mediated drug resistance (CAM-DR)."

sparser
"Our data provide evidence for the relevance of CAM-DR in cisplatin treatment of W1 ovarian cancer cells, both for therapeutically naïve ones or, as a novelty, for those cells that have already developed a genetic resistance mechanism against this antineoplastic drug."

sparser
"Additionally, an enhanced level of VLA4 on MM cells indicates a drug-resistant phenotype xref and is implicated in CAM-DR xref ."

sparser
"Bortezomib (BOR) overcomes CAM-DR by inhibiting VLA-4 [ xref ], and shows a synergistic effect with various drugs in co-culturing human myeloma cell lines with BMSC [ xref ]."

sparser
"In turn, a cell adhesion-mediated drug resistance (CAM-DR) phenomenon occurs."

sparser
"In ALL and chronic lymphocytic leukemia (CLL), adhesion-mediated activation of the PI3K/AKT signaling pathway has been shown to be critical in CAM-DR."

sparser
"Interestingly, W1CR cells also respond to COL1 in the way of CAM-DR, additionally to the intrinsic cisplatin resistance."

sparser
"However, data on the molecular mechanisms underlying the CAM-DR remains scanty."

sparser
"An extracellularly secreted OSF-2 protein could be involved in CAM-DR."

sparser
"This mechanism is designated as a cell adhesion-mediated drug resistance (CAM-DR) [ xref , xref , xref , xref ]."

sparser
"Such an environment can be used to further study the individual or synergic effects of bone marrow extracellular matrix components on CAM-DR against different known or new drugs, or even to develop drugs capable of inhibiting the interaction of mPCs with specific biomolecules."
| PMC

sparser
"The binding of cancer cells to ECM activates the intracellular signals transduction and is designated as a cell adhesion-mediated drug resistance (CAM-DR) [ xref , xref ]."

sparser
"By demonstrating that GBM cells can alternate from one form of CAM-DR (cell-substrate tethering) to another (homocellular cell-cell adhesion) and that inhibition of both forms is necessary for apoptosis sensitization, our findings not only have important implications for novel approaches to restore defective apoptosis programs, but also reveal a novel role of gap junctions in GBM."

sparser
"Interestingly, the interactions between MSCs and LSCs rely on cell-adhesion molecules, such as cadherins and integrins, and are involved in the process of Wnt signaling activation; therefore, CAM-DR plays a critical role in Wnt signaling."

sparser
"One well-established concept of chemotherapy-resistance in leukemia is cell adhesion-mediated drug resistance (CAM-DR)."

sparser
"In conclusion, ANXA7 could promote the cell cycle, proliferation and CAM-DR of MM cells by up-regulating CDC5L."

sparser
"Conclusion and discussion : Our data supports a role for VRK1 in MM cell proliferation, adhesion, and drug resistance, and it may pave the way for a novel therapeutic approach for CAM-DR in MM."

sparser
"It was also reported that CAM-DR induced by the adhesion of MM cells to stromal cells were dominantly mediated by VLA-4 [ xref ]."

sparser
"Schmidmaier and co-authors showed that simvastatin at very low concentrations overcomes CAM-DR in multiple myeloma by geranylgeranylation of Rho proteins and activation of Rho kinase [ xref ]."

sparser
"However, although these findings emphasize CAM-DR in its relevance, our present data have to be discussed and interpreted cautiously, for other ovarian cancer cells, also with respect to other types of ECM matrices, other environmental components, or antineoplastic drugs."

sparser
"Silencing of integrin β7 in MM cells reduces adhesion to fibronectin or E-cadherin, and inhibit CAM-DR of MM cell to bortezomib or melphalan."

sparser
"Another mechanisms of CAM-DR is increasing resistance to detachment-induced cell death (anoikis resistance), and inhibition of FAS-mediated apoptosis [ xref , xref , xref , xref ]."

sparser
"Waldschmidt et al. also evaluated CAM-DR restoration using different antimyeloma agents and the CXCR4 inhibitor plerixafor [ xref ]."

sparser
"However, the molecular mechanisms of CAM-DR and underlying signaling pathways appear elusive."

sparser
"Although these data do not claim a generalization with respect to the in vitro background and the treatment with only one cytotoxic drug, they provide arguments for the process and relevance of CAM-DR in ovarian cancer cells."

sparser
"Fibronectin (FN), a vital ECM component with direct regulatory effects on ECM-mediated anoikis resistance and CAM-DR, making it an attractive and innovative therapeutic target for depriving ECM in tumor tissue."

sparser
"VLA4-nanoparticles hijack cell adhesion mediated drug resistance (CAM-DR) to target refractory myeloma cells and prolong survival."

sparser
"It has been established by multiple studies that cancer cell adhesion to various matrixes is sufficient to confer de novo drug resistance a phenomenon which has been referred to as CAM-DR [ xref – xref ]."

sparser
"Consequently, these findings motivated us to examine the function of VRK1 protein in CAM-DR of MM cells."

sparser
"CAM-DR is crucial to induction of CAM-IR with the subsequent response being a dampening of the immune response through reduced adhesion molecule expression."

sparser
"At present numerous studies have pointed out that Integrin β1 has been reported to be one of the most significant adhesion molecules that has been suggested to be involved in CAM-DR ( xref )."

sparser
"However, in comparison with the significant advances in other strategies for overcoming chemoresistance, progress made with respect to anti CAM-DR therapy has been relatively slow."

sparser
"It becomes clear that both cell lines respond to COL1 binding by an evident increase in EC 50 values, confirming the relevance of ECM substrates for CAM-DR formation in this scenario ( xref a)."

sparser
"The drug resistance that results from direct cell contact with the ECM or other cells has been called “cell-adhesion-mediated drug resistance” or CAM-DR [ xref ]."
| PMC

sparser
"However, these drugs may lose their efficacy because of CAM-DR in refractory MM (RRMM) [ xref – xref ]."

sparser
"Collectively, SOX11 could inhibit tumor proliferation and promote CAM-DR in a CD43 dependent manner."

sparser
"Cell adhesion-mediated drug resistance (CAM-DR) is mainly due to the attachment of tumor cells to the stroma, which may trigger several signal transduction pathways, resulting in reduced sensitivity to anticancer therapies [ xref ]."

sparser
"In this report, we demonstrated for the first time the role of VRK1 in the proliferation and CAM-DR of MM cells."

sparser
"This is comparable to recent studies in other tumor entities showing an interference with integrin signaling as promising targets for sensitization against CAM-DR [ xref ]."

sparser
"Further insights based on these findings are needed to decipher the peculiarities of the underlying molecular mechanisms of CAM-DR in both cell types to generalize the importance of CAM-DR for ovarian cancer cells and for the treatment with other cytotoxic drugs as well."

sparser
"Our previous studies showed that Oroxylin A combined with Paclitaxel reverses cell adhesion mediated-drug resistance (CAM-DR) in HepG2 cells by inhibiting integrinβ1 and PI3K/Akt signaling ( xref )."

sparser
"This kind of resistance, known as cell-adhesion-mediated drug resistance (CAM-DR) is observed both in vivo [ xref ] and in vitro [ xref ], as it was observed in drug-resistant cancer cell lines of breast [ xref ] and ovarian origin [ xref , xref , xref , xref ]."

sparser
"In this study we aimed to elucidate the role of VRK1 in CAM-DR by meddling in its expression using VRK1 shRNA and HA-VRK1 in RPMI 8226 and U266 cell lines."

sparser
"To evaluate CAM-DR as target for sensitization strategies, we analyzed signaling pathways in human estrogen-positive MCF-7 and triple-negative MDA-MB-231 breast cancer cells by western blot, proteome profiler array and TOP-flash assay in presence of COL1."

sparser
"In a recent study, Zhu et al. investigated clinical specimens of ovarian cancer and correlated the expression of CAM-DR related markers, such as CD44, CD147, α5, or β1-integrin subunits with higher resistance and a worse prognosis [ xref ]."

sparser
"This experiment was carried out in a conventional 2D culture at 72 h, varying the dosage from 1 to 1000 µM. The results shown in xref A support the use of a 1000 µM concentration in CAM-DR trials, which produce mortality of around 70%."
| PMC

sparser
"To further study the mechanism by which the combination of WCF and DDP reverses CAM-DR through the Integrin β1 pathway tested the colocalization of Integrin β1 and its ligand proteins by immunofluorescence."

sparser
"These data suggest that MM cells share common regulatory pathways for drug resistance in different models, including SFM-DR and CAM-DR."

sparser
"Considering the key role of CAM-DR for enabling a genetic resistance formation, an insight into the molecular basis of CAM-DR could offer attractive novel targets for an early interference with resistance formation by pharmacological sensitization strategies."

sparser
"Recently, we [ xref , xref , xref , xref ] and others [ xref ] observed the expression of different ECM components in drug-resistant cancer cell lines suggesting their active role in CAM-DR [ xref , xref ]."

sparser
"Cell adhesion mediated drug resistance (CAM-DR) has been strongly linked with the increased abundance of Integrin β3."
| PMC

sparser
"It was an important reason for VRK1 to affect the CAM-DR in MM."

sparser
"Adhesion of ALL cells to BM stromal cells triggers intracellular signals regulating cell adhesion-mediated drug resistance (CAM-DR) ( xref ; xref )."

sparser
"Bortezomib decreased the protein levels of CHD1L, but cell adhesion increased the expression levels of CHD1L, overexpression of CHD1L contributes to cell adhesion-mediated drug resistance (CAM-DR) in multiple myeloma cells [ xref ]."

sparser
"The binding of CXCL12 to its receptor CXC receptor 4 (CXCR4; CD184) will affect cell chemotaxis, cell survival, proliferation, and gene transcription ( xref ). xref found that in multiple myeloma (MM), inhibition of cell adhesion-mediated drug resistance (CAM-DR) caused by bone marrow (BM) is the key to anti-myeloma treatment."

sparser
"Johannes M et al found that interference of CXCL12 and CXCR4 could functionally interfered with MM chemotaxis to the bone marrow (BM), which led to the resensitization of MM cells to drugs by reversing the CAM-DR in MM [ xref ]."

sparser
"The susceptibility of tumor cells adhering to the ECM to a variety of chemotherapeutic drugs is significantly reduced and the drug resistance called cell adhesion-mediated drug resistance (CAM-DR)."

sparser
"To analyze the effects of miR-138 on the expression of small glutamine-rich TPR-containing protein A (SGTA) and cell adhesion-mediated drug resistance (CAM-DR) phenotype in non-Hodgkin's lymphoma (NHL)."

sparser
"Our findings provide evidence for the importance of different CAM-DR mechanisms depending on the respective breast cancer cells and reveal potential targets originating from the integrin signaling routes."

sparser
"While multiple factors play a role in myeloma carcinogenesis, the Very Late Antigen 4 (VLA4, CD49d/CD29, integrin α 4 β 1 ) is a front-runner implicated in myeloma cell homing, survival and acquisition of cell-adhesion mediated drug resistance (CAM-DR)."

sparser
"At a functional level, the link between ECM binding and loss of chemosensitivity of BC refers to the phenomenon of cell-adhesion-mediated drug resistance (CAM-DR)."

sparser
"Cell adhesion-mediated drug resistance (CAM-DR)."

sparser
"As we observed, reduced protein phosphorylation resulting probably in reduced signal transduction, reduced number of CSCs, decreased expression of drug transporters, and decreased expression of ECM molecules, resulting likely in reduced CAM-DR."

sparser
"Targeting CAM-DR and Mitochondrial Transfer for the Treatment of Multiple Myeloma."

sparser
"CAM-DR, which has initially been described in multiple myeloma and other malignancies of hematopoietic origin [ xref ], also appears relevant for different solid tumor entities [ xref , xref , xref ]."

sparser
"The interplay between cancer cells and the tumor microenvironment via cell adhesion molecules (CAMs) promotes drug resistance, known as cell adhesion-mediated drug resistance (CAM-DR)."

sparser
"Given the known concept of CAM-DR we assessed whether factors with implications in intercellular contact or signaling were dysregulated."

sparser
"These data indicate that ITGB1-driven CAM-DR is a clear factor for cisplatin resistance in W1 cells when they are in contact with COL1."

sparser
"Thus, targeting the ECM, Integrins and the interaction between them in CAM-DR might be an effective method to control cancer chemoresistance."

sparser
"CD44 upregulates the expression of cell cycle proteins inhibitors, anti-apoptotic proteins, and ABC transporters, and others, thus inducing a form of drug resistance known as cell adhesion-mediated drug resistance (CAM-DR)."

sparser
"One study explained the role of CAM-DR on modulation of cancer cell adhesion on ECM in multiple myeloma showing that the adhesion resulted in increased p27kip1 levels that associated with cell cycle arrest and resistance to melphalan (Hazlehurst and Dalton xref )."

sparser
"In terms of the environmentally-mediated communication of tumor cells, CAM-DR is meanwhile considered as an important initial trigger mechanism to escape apoptosis by a rapid, non-genetically based adaptation [ xref ]."

sparser
"MM is considered to be uncurable because MM cells are protected by the BM microenvironment, including CAM-DR, SFM-DR, vascular and endosteal niches, and clonal evolution leads to refractoriness for chemotherapy."

sparser
"CD44 upregulates the expression of ABC transporters, thereby inducing a form of drug resistance known as cell adhesion-mediated drug resistance (CAM-DR) ( xref )."

sparser
"In CAM-DR model, both SOX11 and CD43 in MCL cells were elevated when co-cultured with M2-10B4 bone marrow fibroblasts or fibronectin."

sparser
"Indeed, an earlier study has shown that VLA-4 plays a critical role in CAM-DR of MM cells, and that combination of bortezomib with conventional anti-MM drugs may be effective in overcoming CAM-DR [ xref ]."

sparser
"Cell adhesion-mediated drug resistance (CAM-DR) is induced by the adhesion of tumor cell integrins to stromal fibroblasts or to components of the extracellular matrix, such as fibronectin, laminin, and collagen [ xref ]."

sparser
"IGF-1, which are secreted from BMSC and autocrined by MM cells, binds with IGF-1R, contributing to the proliferation of myeloma cells and CAM-DR [ xref , xref ]."

sparser
"Finally, the microenvironment, such as CAM-DR, hypoxia, and the endosteal niche, contributes to the survival of MRD and MM stem cells."

sparser
"This study aimed to investigate whether annexin A7 (ANXA7) could promote the cell cycle, proliferation and cell adhesion-mediated drug resistance (CAM-DR) of multiple myeloma (MM) cells by up-regulating cell division cycle 5-like (CDC5L)."

sparser
"These molecular interactions suggest that the heterodimer α2β1 contributes to CAM-DR."
| PMC

sparser
"VRK1 acts as a negative factor of CAM-DR in MM."

sparser
"These findings point towards a novel PTK2B-LPXN axis in CAM-DR by altered niche interactions in the context of LSC properties in FLT3-ITD AML."

sparser
"Bortezomib decreases α4β1 expression and results in inhibition of CAM-DR in MM a finding that may contribute to the clinical success of bortezomib [ xref ]."

sparser
"CAM-DR is considered as the onset for resistance mutations, but underlying mechanisms remain elusive."

sparser
"Furthermore, we clarified that CD49d- and CD49e-mediated CAM-DR could be attributed to an increase in the expression of B cell leukemia-xL (Bcl-xL) and survivin proteins, and a decrease in the expression of Bcl-2 associated X (Bax), Bcl-2 interacting mediator (Bim) and p53 upregulated modulator of apoptosis (PUMA) proteins via nuclear factor kappaB (NF-κB) activation."

sparser
"Finally, it was revealed that HSPA12B overexpression enhances CAM-DR."

sparser
"Additionally, ECM proteins can induce cell adhesion mediated drug resistance (CAM-DR), leading to increased resistance to apoptosis [ xref ]."

sparser
"Shain et al.showed that drug resistance of myeloma cell lines correlates with increased adherence potential (i.e., CAM-DR), via either increased VLA4 expression or shift from low- to high- affinity state xref , xref , xref ."

sparser
"The string database predicts that ANXA7 can combine with CDC5L. Therefore, we further hypothesized that ANXA7 interference could promote cell cycle arrest in G2/M phase through CDC5L to inhibit proliferation of MM cells and reduce cell adhesion-mediated drug resistance (CAM-DR)."

sparser
"Heterodimeric complexes, such as integrin α4/β1 dimer, have been linked to cell adhesion-mediated drug resistance (CAM-DR) to EGFR inhibitors (cetuximab) [ xref ]."

sparser
"Although the acquired resistance is only moderate, CAM-DR is considered as essential prerequisite to confer a prolonged survival of tumor cells towards antineoplastic agents and thus favors the acquisition of genetic drug resistance mechanisms [ xref ]."

sparser
"Although those protumorigenic effects of integrins in breast cancer have not been considered in terms of CAM-DR, a link between integrins and malignancy of breast cancers could be elucidated."

sparser
"The PI3K-Akt signaling pathway is involved in rituximab action, chronic activation of BCR signaling, and CAM-DR."

sparser
"To understand these mechanisms, this review focuses on the role of CD44, cadherins, selectins, and integrins in CAM-DR in endocrine-related cancers."

sparser
"Notably, the COL1 induced CAM-DR adds as an independent process to the pre-existing cisplatin resistance in W1CR cells, which is a novel and unexpected finding improving our understanding."

sparser
"The molecular interaction between tumor cells and microenvironment is considered to be the onset of chemotherapy resistance, namely cell adhesion mediated drug resistance (CAM-DR)."

sparser
"However, the role of VLA-1 in CAM-DR in leukemia is still unknown."

sparser
"However, these differences are not significant enough to attribute to hyaluronic acid and collagen a CAM-DR effect against BRZ, as occurs with DEX."
| PMC

sparser
"The α4β1 integrin is a main adhesion receptor mediating MM cell-stroma interactions and MM cell survival, and its expression and function are downregulated by BTZ, leading to inhibition of cell adhesion-mediated drug resistance (CAM-DR) and MM cell apoptosis."

sparser
"Furthermore, they can induce drug resistance in surrounding cells by CAM-DR [ xref ]."

sparser
"Consistent with this prediction, CAM-DR involves signaling through MEK/ERK and FAK pathways (Dickreuter and Cordes, xref ) and in breast cancer, upregulation of Teneurin-related Tenascin-C was implicated (Jansen et al., xref )."

sparser
"Furthermore, several other signaling pathways including MAP/ERK [ xref , xref ], Wnt3/RhoA/ROCK [ xref ], and HMG-CoA/Rho/Rho-kinase [ xref ] are involved in CAM-DR of MM."

sparser
"Aiming to elucidate the relevance and underlying mechanisms of CAM-DR in ovarian cancer cells, the present study investigates the role of collagen binding of W1 ovarian cancer cells with respect to cisplatin sensitivity."

sparser
"We were able to simulate CAM-DR by showing a decrease in sensitivity of human MCF-7 and MDA-MB-231 breast cancer cells to MX or CDDP cytotoxicity when cells were cultivated in presence of COL1."

sparser
"Whether this contributes to cell adhesion‐mediated drug resistance (CAMDR) has to be further elucidated. xref "

sparser
"We also examined the therapeutic targets of CAM-DR in BL cells and found CD49d and CD49e to be the important adhesion molecules involved."

sparser
"Cellular adhesion-mediated drug resistance (CAM-DR) is one of the underlying mechanisms of disease relapse and refractoriness to antimyeloma therapy [ xref ]."

sparser
"Pazopanib may find use as a CAM-DR inhibitor as it inhibits VEGF-induced up-regulation of adhesion molecules on tumor cells [ xref ]."

sparser
"In the W1PR2 cell line, the strength of CAM-DR can result from dephosphorization signaling molecules by PTPRK and stimulation of CAM-DR by extracellular COL3A1."

sparser
"In tumor tissue, other mechanisms of drug resistance such as cell adhesion mediated drug resistance (CAM-DR) can be developed [ xref ]."