The tumor microenvironment: focus on myeloma.
A wide variety of cellular responses that may afford tumor cells drug-tolerance characteristics. Overexpression of plasma membrane efflux pumps, up-regulation of anti-apoptosis factors, down-regulation of proapoptosis factors, subcellular redistribution of drug targets, and up-regulation of detoxifying enzymes are just a few known mechanisms of cancer cell resistance. In addition to these individual cell adaptations, cellular drug resistance also appears to be mediated by the binding of tumor cells to extracellular matrix (ECM) proteins. Cell adhesion-mediated drug resistance (CAM-DR) is particularly relevant in hematologic malignancies such as multiple myeloma, where myeloma cells localize in the bone marrow and interact with stroma and stromal cells, initiating the production of proteins that stimulate or support tumor survival. Thus, CAM-DR provides a plausible explanation for the protective mechanisms associated with myeloma cell adhesion and demonstrates that the tumor microenvironment may hold the key to elucidating how tumor cells resist chemotherapy.
Dalton
William S
WS
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. dalton@moffitt.usf.edu
D017209:Apoptosis / Q000502:physiology*; D001853:Bone Marrow / Q000473:pathology / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology*; D002470:Cell Survival; D003546:Cysteine Endopeptidases / Q000494:pharmacology; D004250:DNA Topoisomerases, Type II / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009101:Multiple Myeloma / Q000503:physiopathology*; D046988:Proteasome Endopeptidase Complex; D015398:Signal Transduction; D015854:Up-Regulation; D019014:fas Receptor
D009097:Multienzyme Complexes; D019014:fas Receptor; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D004250:DNA Topoisomerases, Type II