Substrate spectrum of matrix metalloprotease-2 in physiology and pathology

Matrix metalloproteases (MMPs) are a family of extracellular proteases (enzymes) which reside outside cells and initiate the breakdown of proteins that mediate cellular signals. Processing by MMPs can activate, deactivate, or functionally convert signaling proteins. Within the MMP family, MMP-2 plays a pivotal role in cancer spread, since collagen IV degradation by MMP-2 allows tumor cells to penetrate the surrounding tissue. While MMP-2 is an attractive drug target for cancer treatment, clinical trials have shown that drugs which interfere with this enzyme cause severe side effects, partly because the protease is believed to play a part in so many other cell functions. Dr. Oliver Schilling is using innovative proteomic tools to identify and characterize novel MMP-2 substrates on a system-wide scale. His project aims to identify the abundant variety of natural substrates of MMP-2 as well as to the roles of MMP-2 and the cellular signaling pathways that the protease regulates. Given the prominent role of MMP-2 in tumor development, this knowledge has the potential to assist in the development of cancer drugs which are more effective and have fewer side effects.