Mechanisms associated with cell adhesion mediated drug resistance (CAM-DR) in hematopoietic malignancies.
Cancer Metastasis Rev
; 20(1-2): 43-50, 2001.
Article
in En
| MEDLINE
| ID: mdl-11831646
ABSTRACT
The tumor microenvironment is often overlooked when considering tumor response to chemotherapeutic agents. This environment consists of soluble factors, components of the extracellular matrix as well as cell-cell interactions. Recently, it has become clear that cell-cell and cell-matrix interactions result in cytoskeletal reorganization and the activation of multiple signal transduction pathways that directly influence cell survival, growth and differentiation. Experimental evidence shows that anti-apoptotic pathways initiated by cell adhesion are operative in tumor cells and, furthermore, cause resistance to mechanistically distinct cytotoxics. For hematopoietic tumors, cell adhesion to a single matrix, fibronectin is sufficient to inhibit apoptosis induced by mechanistically distinct cyctotoxics. Adhesion of hematopoietic tumors to this matrix blocks cell cycle progression, and for the human multiple myeloma 8226 cell line adhesion to fibronectin resulted in increased p27kip1 levels, which correlated with cell cycle arrest and drug resistance. A decrease in initial DNA damage induced by topoisomerase II inhibitors has also been observed in adherent hematopoietic tumor cell lines. Further studies investigating the mechanisms of cell adhesion mediated drug resistance may reveal novel targets directed at the reversal of de novo drug resistance.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Adhesion
/
Fibronectins
/
Drug Resistance, Neoplasm
/
Multiple Myeloma
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Cancer Metastasis Rev
Journal subject:
NEOPLASIAS
Year:
2001
Document type:
Article
Affiliation country:
Estados Unidos