MMPs as Regulators of Tumor Microenvironment

Matrix metalloproteinases (MMPs) are a family of zinc‐dependent endopeptidases with important functions in development, tissue injury and repair and cancer. In cancer MMPs pave the way for tumor cell invasion and metastasis through extracellular matrix degradation as well as with non‐protelytic functions. Due to their ability to cleave, degrade and rearrange ECM molecules, MMPs can modulate a variety of stem cell niches both normal and in neoplastic progression. Indeed, changes in the microenvironment such as overexpression of an MMP can alter the propensity of signaling pathways that promote stem cell expansion and alter neoplastic risk. The abilities of MMPs to influence differentiation processes may be hijacked in cancer. There are also several ways by which MMPs may be influence proliferation during development and also in the tumor microenvironment, since they can alter the bioavailability or functionality of multiple important growth regulating factors. MMPs contribute to tissue invasion based on their ability to cleave ECM and basement membrane components proteolytically, and thereby pave the way through the interstitium for invading tissues or cancer cells. However, not all MMP functions are pro‐cancer. MMP8 may protect from tumor progression. Thus use of inhibitors tthat are specific for particular MMPs, e.g,, antibodies may have promise in the long run therapeutically. Supported by grants from NCI