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Implication of Tumor Microenvironment in Chemoresistance: Tumor-Associated Stromal Cells Protect Tumor Cells from Cell Death
EA4553, Institut Claudius Regaud, F-31062 Toulouse, France and University of Toulouse III, Toulouse F-31052, France
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 8 June 2012; in revised form: 13 July 2012 / Accepted: 17 July 2012 / Published: 30 July 2012
Abstract: Tumor development principally occurs following the accumulation of genetic and epigenetic alterations in tumor cells. These changes pave the way for the transformation of chemosensitive cells to chemoresistant ones by influencing the uptake, metabolism, or export of drugs at the cellular level. Numerous reports have revealed the complexity of tumors and their microenvironment with tumor cells located within a heterogeneous population of stromal cells. These stromal cells (fibroblasts, endothelial or mesothelial cells, adipocytes or adipose tissue-derived stromal cells, immune cells and bone marrow-derived stem cells) could be involved in the chemoresistance that is acquired by tumor cells via several mechanisms: (i) cell–cell and cell–matrix interactions influencing the cancer cell sensitivity to apoptosis; (ii) local release of soluble factors promoting survival and tumor growth (crosstalk between stromal and tumor cells); (iii) direct cell-cell interactions with tumor cells (crosstalk or oncologic trogocytosis); (iv) generation of specific niches within the tumor microenvironment that facilitate the acquisition of drug resistance; or (v) conversion of the cancer cells to cancer-initiating cells or cancer stem cells. This review will focus on the implication of each member of the heterogeneous population of stromal cells in conferring resistance to cytotoxins and physiological mediators of cell death.
Keywords: microenvironment; cancer; chemoresistance; apoptosis
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Castells, M.; Thibault, B.; Delord, J.-P.; Couderc, B. Implication of Tumor Microenvironment in Chemoresistance: Tumor-Associated Stromal Cells Protect Tumor Cells from Cell Death. Int. J. Mol. Sci. 2012, 13, 9545-9571.
Castells M, Thibault B, Delord J-P, Couderc B. Implication of Tumor Microenvironment in Chemoresistance: Tumor-Associated Stromal Cells Protect Tumor Cells from Cell Death. International Journal of Molecular Sciences. 2012; 13(8):9545-9571.
Castells, Magali; Thibault, Benoît; Delord, Jean-Pierre; Couderc, Bettina. 2012. "Implication of Tumor Microenvironment in Chemoresistance: Tumor-Associated Stromal Cells Protect Tumor Cells from Cell Death." Int. J. Mol. Sci. 13, no. 8: 9545-9571.