How matrix metalloproteinases regulate signaling in cancer

Matrix metalloproteinases (MMPs) have many functions in the cellular microenvironment through cleavage of proteins leading to their activation, inactivation or removal. As a result broad‐spectrum inhibitors of these enzymes were unsuccessful in clinical trials in cancer patients. We have examined the nature of protumorigenic and antitumorigenic targets and functions of MMPs. Our data indicate that MMP9, MMP13 and MMP14 dependent remodeling of the collagen scaffold regulates angiogenesis, tumor cell invasion and migration and inflammatory cell infiltration. The outcomes vary with oncogenes, tumor type and location. MMPs increase VEGF bioavailability and also increase production of antiangiogenic extracellular matrix fragments.