IndraLab
Statements
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
"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
"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
"Some of the factors involved in the acquisition of anti-cancer drug resistance, as well as the MDR conversion phenomena, include ATP-dependent transporters (e.g., MRP-1), which sense and expel anti-cancer drugs out of the cells ( xref ), anti-apoptotic factors such as Bcl-2, which promotes cell survival and defends against drug-induced apoptosis ( xref , xref ), the induction of drug detoxification mechanisms ( xref ), and cell adhesion-mediated drug resistance (CAM-DR), in which chemotherapy-induced apoptosis is suppressed when cancer cells adhere to the extracellular matrix, increasing their resistance to chemotherapy ( xref )."
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
"CAM-DR is a mechanism in which MM cells escape the cytotoxic effects of anticancer therapy through adhesive interactions with BMSCs and/or ECM components using integrin family adhesion molecules (i.e., CD138/syndecan-1, Vascular Cell Adhesion Molecule-1/VCAM-1, Very Late Activation Antigen/VLA4/α4β1, VLA-5/α5β1, αvβ3 and β7 integrins) [ xref ]."
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
"Paradigmatic for DLBCL is the intricate interplay of factors such as lymphatic infiltration, angiogenesis, cell adhesion-mediated drug resistance (CAM-DR), tumor microenvironment and tumor progression that may contribute to the development of chylous effusions [ xref , xref , xref , xref ]."
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
"Several cell adhesion molecules (VLA-4 and VLA-5, for instance), soluble factors (such as IL-6) and extracellular matrix components (for example, fibronectin) have been shown to be relevant during BM-ME and MM cell interactions and responsible for MM cell survival and importantly, for the so-called cell adhesion-mediated drug resistance (CAM-DR) [ xref , xref , xref , xref ]."
sparser
"However, the molecular basis of MM progression and drug resistance are not completely understood. xref , xref Mounting evidence now suggests that the direct adhesive interactions between MM cells and the bone marrow (BM) microenvironment, also known as ‘cell adhesion mediated drug resistance’ (CAM-DR), play a critical role in tumor development."
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
"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
"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
"In the BM microenvironment, a proportion of the myeloma cells are insensitive to chemotherapy, which is the main cause of drug resistance and relapse. xref , xref , xref It was reported that the cell cycle of MM cells was arrested at the G 0 /G 1 phase when myeloma cells were co-cultured with BM stromal cells, wherein the main feature of the cells was quiescence. xref , xref Moreover, p27 accumulation has been associated with the CAM-DR phenotype and could represent a new class of drug-resistance genes. xref We, therefore, hypothesized that RBX1 is a likely candidate for regulating p27 ubiquitination and proteasomal degradation in adherent myeloma cells."
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
"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
"The resulting increase in the p27kip1 protein level inhibits cyclin A- and cyclin E-dependent CDK2 kinase activity [ xref , xref , xref ], generating a G0/G1 cell cycle arrest and thus an intrinsic drug resistance to dexamethasone (DEX) in the RPMI8226 MM cell line [ xref ], known as cell adhesion-mediated drug resistance (CAM-DR) [ 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
"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
"This work aims to develop a 3D culture system based on a microgel made up of poly(ethyl acrylate) copolymers functionalized with ECM biomolecules, such as FN, and capable of mimicking both the bone marrow microenvironment by interacting with the tumor cells and the CAM-DR effect generated by the biomolecules."
sparser
"However, due to the downregulation of VLA-4 produced by BRZ [ xref ], it was found that the MFN-RPMI condition, which showed an initial resistance to DEX, overcame this CAM-DR effect and presented higher mortality than the FN condition with only DEX, confirming that the resistance was generated by the CAM-DR effect of FN."
sparser
"After confirming that the culture in the microgel allowed the cells to interact with the functionalized biomolecule on the microspheres’ surfaces, the microgel was tested for interference with the drug assays by evaluating the CAM-DR effect of FN against high-dose DEX and BRZ, two of the drugs used against MM in clinical practice."
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
"In particular, myeloma cell adhesion to BMSCs supports cell survival, proliferation, and cell adhesion-mediated drug resistance (CAM-DR) via signaling pathway activation, including the NF-kB (nuclear factor-kB), JAK/Stat3 (Janus kinase/signal transducer and activator of transcription-3), and MEK/MAPK (mitogen activated protein [MAP] kinase kinase/MAP kinase) pathways [3–5]."
sparser
"CAFs form the major constituents of TME, and they are intricately linked to the induction of tumour cell chemoresistance. xref The CAF‐driven tumour chemoresistance can be divided into two categories: via cell adhesion mediated drug resistance (CAM‐DR), and via release of soluble and secretory factors mediated drug resistance (SFM‐DR)."
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
"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
"More specifically,exhaustively described in their review the interactions between tumour cells and extracellular matrix components, including both filamentous proteins (laminin, fibronectin, and collagen) and paracrine factors (cytokines, chemokines, growth factors, exosomes), involved together in the process of cell adhesion-mediated resistance (CAM-DR), essential in different tumours including multiple myeloma, non-Hodgkin’s lymphoma, leukaemia and solid tumours."
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
"The direct cell adhesion contact through adhesion molecules such as very late antigen 4 (VLA-4), vascular cell adhesion protein, lymphocyte function-associated antigen-1, and intercellular adhesion molecule 1 stimulates IL-6 secretion by BMSCs [ xref ] and mediates drug resistance through cellular-adhesion-mediated drug resistance (CAM-DR) [ xref ]."
sparser
"The SDF-1α/CXCR4 axis mediates drug resistance through different pathways that are involved in CAM-DR, affecting adhesion molecules, enhancing IL-6 mediated drug resistance, and stimulating pathways including MAP/extracellular signal-regulated kinase (ERK), wingless/integrated3 (Wnt3)/Ras homolog family member A/Ras homologous -associated protein kinase, and Ras homologous/Ras homologous -kinase [ xref , xref , xref , xref , xref ]."
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
"ECM, such as laminin, fibronectin, vimentin, mediated interactions between cells and participated in signal transduction in processes such as cell adhesion, migration, invasion, proliferation and EMT to promote the development of drug resistance, referred to as cell adhesion mediated drug resistance (CAM-DR) (Baltes et al. xref ; Valkenburg et al. xref )."
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
"Given the emerging key role of the BM microenvironment in AML, the identification of new therapeutic interventions to overcome cell adhesion-mediated drug resistance (CAM-DR) requires the development of in vitro co-culture models that recreate the in vivo BM setting for studies of the biology of AML, as well as for drug screening [ xref ]."
sparser
"Two categories of BM-related DR exist, namely cell adhesion mediated DR (CAM-DR), caused through the interactions between the MM cells and the cellular compartment (BM stromal cells, endothelial cells, osteoblasts, osteoclasts, and immune cells) and/or extracellular matrix, and soluble factor mediated DR (SFM-DR), caused through the interactions between the MM cells and the non-cellular compartment (cytokines, growth factors, chemokines, and exosomes) ( xref , 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
"Increased interactions between adhesion molecules of ECM (e.g., fibronectin, E-cadherin, or laminin) and integrins, heparin sulfate proteoglycans, or surface signal receptors on tumor cells results trigger anti-apoptotic properties of MM cells, leading to cell-adhesion–mediated drug resistance (CAM-DR) [ xref , xref ]."
sparser
"Earlier literature suggests that different adhesion molecules including integrin and non-integrin proteins are aberrantly expressed on the surface of neoplastic MM cells, which aid in the homing of MM cells to the BM stromal cells and develop CAM-DR (Additional file xref : Table S3)."
sparser
"For instance, interaction between acute myelogenous leukemia and fibronectin in bone marrow reduces chemosensitivity of the cells [ xref ] and the chemoresistance mediated by receptor–ligand interaction of the cells with ECM is termed as cell-adhesion-mediated drug resistance (CAM-DR) [ xref ]."
sparser
"Finally, oligonucleotide microarray analysis showed that 11 of the 53 genes whose expression was induced by FN adhesion have been reported to be regulated by the NF-kB family of transcription factors, suggesting that NF-kB family members, especially RelB-p50 heterodimers, are key factors of signal transduction that mediate CAM-DR [89]."
sparser
"The SFM-DR is mediated by CAF-produced cytokines, chemokines, growth factors, exosomes, and desmoplastic reactions, which protect cancer cells against drug-induced apoptosis, while the CAM-DR is mediated by the adhesion of cancer cell integrins to stromal fibroblasts or to components of the ECM, such as fibronectin, collagen, and laminin."
sparser
"For instance, CCT1 and CCT2 were essential in the survival of breast cancer patients; xref CCT2 and CCT5 were found to be overexpressed in colorectal cancer tissues; xref CCT3 was indispensable for proper mitotic progression, while CCT3 inhibition increased susceptibility in HCC patients undergoing chemotherapy; xref CCT8 was found to play a role in the development of B-cell non-Hodgkin’s lymphoma and overexpression of CCT8 could reverse cell adhesion-mediated drug resistance (CAM-DR). xref Recently, special attention has been given to CCT6A for its different roles in cancer."
sparser
"In tumor cells, aberrant cell ‐ECM interaction elicits altered signal transduction and often results in resistance to chemotherapy drugs or molecular agents, and is known as cell adhesion‐mediated drug resistance (CAM‐DR). [ xref ] IDH1 and OCT6 showed enhanced binding at the canonical focal adhesion target gene, COL6A1 (Figure xref ), which was further supported by the ChIP analysis (Figure xref ; Figure xref , Supporting Information)."
sparser
"CAM-DR is induced by adhesion molecules such as integrin family members [ xref , xref ], CD138 (syndecan-1) [ xref ], CD44 [ xref ], vascular cell adhesion molecule-1 (VCAM-1) [ xref ], lymphocyte function-associated antigen-1 (LFA-1) [ xref , xref ], and intercellular adhesion molecule-1 (ICAM-1) [ xref ]."
sparser
"Importantly, the adhesion of MM cells to BMSCs and/or the extracellular matrix triggers the NF-κB-dependent transcription and secretion of cytokines such as IL-6, tumor necrosis factor-α, and osteopontin in BMSCs, which further stimulates development of drug resistance or so-called cell adhesion-mediated drug resistance (CAM-DR) [ xref , 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
"The aberrant adhesion of tumor cells to the ECM shields them from cytotoxic injury caused by chemotherapeutic drugs or molecular targeted agents, thus leading to the development of cell adhesion‐mediated drug resistance (CAM‐DR). [ xref ] As such, therapeutic strategies that impede focal adhesion maybe an ideal starting point for drug development."
sparser
"By facilitating the interaction between tumor cells and stromal cells, CXCR4 may also play a role in cell adhesionmediated drug resistance of tumor cells (CAM-DR) Moreover, the rationale, mode of use and the type of CXCR4 antagonist may change depending on the type of cancer and patient condition."
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
"MM cells interact with components in the BM microenvironment to support their own survival and growth. [ xref ] Specifically, MM cells adhere to the extracellular matrix or BMSCs in the bone marrow through adhesion molecules, such as integrin family members, [ xref ] CD138, [ xref ] CD44, [ xref , xref ] vascular cell adhesion molecule‐1, [ xref ] lymphocyte function‐associated antigen‐1, [ xref ] and intercellular adhesion molecule‐1, [ xref ] leading to the enhancement of their survival and CAM‐DR."
sparser
"However, since cyclin D1 expression enhances MM cell adhesion to stromal cells and fibronectin, favors cell migration, and increases chemotaxis as well as inflammatory chemokine secretion, CFZ-mediated resistance was alleviated particularly in cyclin D1 expressing cells by the immunomodulatory drugs, which modify MM–TME interactions, such as CAM-DR ( xref )."
sparser
"The ECM receptor interactions were shown to induce cell adhesion‐mediated drug resistance (CAM‐DR) in EOC. xref Januchowski et al. xref reported that the extracellular matrix (ECM) could affect drug resistance progression in ovarian cancer by prohibiting the drug penetration into cancer cells and developing resistance to apoptosis."
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
"Among those, CD44 has been reported as a key cell adhesion–mediated drug resistance (CAM-DR) xref molecule and is a known mediator of tumor-BME interactions. xref , xref In line with the differential gene expression analysis, a coaccessibility analysis of the scATAC-seq data showed a strong correlation between the CD44 promoter and a distal putative enhancer element for subclone 1 that was absent for subclone 2 at time point T1 ( xref D)."
sparser
"This result is somewhat surprising as HA survival activity is associated with increased cell cycle progression and down-regulation in the expression of p27kip1 cyclin-dependent kinase inhibitor, whereas the FN-induced CAM-DR phenotype results in a G1 arrest associated with increased p27kip1 protein levels [3,78]."
sparser
"In particular, integrin α4 is expressed in B-ALL cells ( xref ) and has been previously implicated in CAM-DR which serves a key role in tumor microenvironment ( xref ), since the binding of α4 to its ligand VCAM-1 mediates signaling to maintain the survival of leukemic cells in the presence of chemotherapy ( xref , xref , xref )."
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
"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
"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
"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
"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
"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
"This innovative approach, facilitated by the
Single-probe,
offers a solution for the rapid and reliable prediction of drug-resistant
cancer cell phenotypes such as those associated with chemoresistance
mechanisms (e.g., cell adhesion-mediated drug resistance (CAM-DR)). xref Advanced data analysis, incorporating machine
learning algorithms, was subsequently used to process complex metabolomic
data."
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
"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
"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
"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
"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
"This ECM-mediated chemoresistance mechanism is primarily based on activation of integrin signaling, which results in overexpression of prosurvival and antiapoptotic proteins, cell cycle arrest, modulation of drug efflux, and a phenotype switching of cancer cells (e.g., EMT or cancer stemness), which is referred to as cell adhesion-mediated drug resistance (CAM-DR) [ xref ]."
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
"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
"AML cells express integrins which bind to ligands in the microenvironment enabling adhesion of leukemia cells to microenvironment thereby initiating intracellular signaling pathways that are associated with cell migration, cell proliferation, survival, and drug resistance which has been described to mediate cell-adhesion mediated drug-resistance (CAM-DR)."
sparser
"In addition, the chemotherapy resistance mechanism mediated by ECM is mainly based on the activation of integrin signaling, which leads to overexpression of pro-survival and anti-apoptotic proteins, cell cycle arrest, regulation of drug efflux, and phenotype transition of cancer cells (such as EMT or cancer stemness), which is called cell adhesion-mediated drug resistance (CAM-DR) [ xref ]."
sparser
"EPHB6, a kinase-defective Eph receptor, belongs to the human receptor tyrosine kinase family and appears to function as a malignancy-suppressing factor and inhibitor of metastasis, which regulates cell adhesion and migration. xref , xref Additionally, EPHB6 mutation promotes cancer cell proliferation and migration/invasion and induces cell adhesion-mediated drug resistance (CAM-DR), such as paclitaxel-resistance. xref The TMEM100 (Transmembrane protein 100) gene maps to chromosome 17q32 and encodes a 134-amino acid protein predicted to have two transmembrane domains."