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 ECM 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 epigenetically silenced in different
cancers. The importance of these
proteases in modifying the tumor microenvironment highlights the need for a deeper understanding of how stroma cells and the ECM can modulate
tumor progression.