The Extracellular Matrix and the Growth and Survival of Tumors
The role of the extracellular matrix (ECM) in the tumor microenvironment extends well beyond the formation of a barrier against tumor invasion. Through a combination of physical forces and chemical signals generated upon contact between cells and ECM proteins, the ECM exerts a control on the proliferation and survival of cancer cells, which were previously considered to be solely affected by genetic alterations. The interaction between tumor cells and the ECM is also a dynamic one that changes upon modification of the ECM by proteases produced by tumor cells and by normal cells in the tumor microenvironment. These proteases modify the ECM generating cryptic epitopes, producing proteolytic fragments that are biologically active and releasing growth factors and cytokines that are trapped in the ECM. Our knowledge of the mechanisms by which the ECM controls cancer cells has significantly improved over the last 10 years and is now leading toward clinical trials testing agents disrupting tumor cell–ECM interaction.
KeywordsCollagen Type Zoledronic Acid Focal Adhesion Kinase Proteolytic Modification Proteolytic Fragment
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