Journal
PHARMACOLOGY & THERAPEUTICS
Volume 141, Issue 2, Pages 192-208Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2013.10.003
Keywords
Extracellular matrix; Matrix metallo proteinases; Angiogenesis; Immune cells; Cancer associated fibroblasts; Tumor microenvironment
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Funding
- European Research Council [232640-IMAGO]
- European Commission
- National Institutes of Health [R01 CA75334]
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Cancer cells rely on extensive support from the stroma in order to survive, proliferate and invade. The tumor stroma is thus an important potential target for anti-cancer therapy. Typical changes in the stroma include a shift from the quiescence promoting-antiangiogenic extracellular matrix to a provisional matrix that promotes invasion and angiogenesis. These changes in the extracellular matrix are induced by changes in the secretion of extracellular matrix proteins and glucose amino glycans, extravasation of plasma proteins from hyperpermeable vessels and release of matrix modifying enzymes resulting in cleavage and cross-linking of matrix macromolecules. These in turn alter the rigidity of the matrix and the exposure and release of cytokines. Changes in matrix rigidity and vessel permeability affect drug delivery and mediate resistance to cytotoxic therapy. These stroma changes are brought about not only by the cancer cells, but also through the action of many cell types that are recruited by tumors including immune cells, fibroblasts and endothelial cells. Within the tumor, these normal host cells are activated resulting in loss of inhibitory and induction of cancer promoting activities. Key to the development of stroma-targeted therapies, selective biomarkers were developed for specific imaging of key aspects of the tumor stroma. (C) 2013 Elsevier Inc. All rights reserved.
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