AUTHOR=Noël Agnès 

TITLE=New and Paradoxical Roles of Matrix Metalloproteinases in the Tumor Microenvironment

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 3 - 2012

YEAR=2012

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2012.00140

DOI=10.3389/fphar.2012.00140

ISSN=1663-9812

ABSTRACT=Processes such as cell proliferation, angiogenesis, apoptosis or invasion are strongly influenced by the surrounding microenvironment of the tumor. Therefore, the ability to change these surroundings represents an important property through which tumor cells are able to acquire specific functions necessary for tumor growth and dissemination. Matrix metalloproteinases (MMPs) constitute key players in this process, allowing tumor cells to modify the extracellular matrix (ECM) and release cytokines, growth factors and other cell surface molecules, ultimately facilitating protease-dependent Processes such as cell proliferation, angiogenesis, apoptosis or invasion are strongly influenced by the surrounding microenvironment of the tumor. Therefore, the ability to change these surroundings represents an important property through which tumor cells are able to acquire specific functions necessary for tumor growth and dissemination. Matrix metalloproteinases (MMPs) constitute key players in this process, allowing tumor cells to modify the extracellular matrix (ECM) and release cytokines, growth factors and other cell surface molecules, ultimately facilitating protease-dependent tumor progression. Remodeling of the extracellular matrix by collagenolytic enzymes such as MMP1, MMP8, MMP13 or the membrane-bound MT1-MMP as well as by other membrane-anchored proteases is required for invasion and recruitment of novel blood vessels. However, the multiple roles of the MMPs do not all fit into a simple pattern. Despite the pro-tumorigenic function of certain metalloproteinases, recent studies have shown that other members of these families, such as MMP8 or MMP11, have a protective role against tumor growth and metastasis in animal models. These studies have been further expanded by large-scale genomic analysis, revealing that the genes encoding metalloproteinases, such as MMP8, MMP27, ADAM7 and ADAM29, are recurrently mutated in specific tumors, while several ADAMTSs are epigenetical