Metalloproteinases Help Regulate Blood Vessel Formation

Researchers have found that the membrane bound matrix metalloproteinase enzyme (MT1-MMP) contributes to blood vessel formation and is, therefore, an attractive target for chemotherapy through regulation of platelet-derived growth factor-beta (PDGF-beta) signaling.

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases, which are capable of collectively degrading all kinds of extracellular matrix proteins, but also can process a number of bioactive molecules. The MMPs play an important role in tissue remodeling associated with various physiologic and pathologic processes such as morphogenesis, angiogenesis, tissue repair, cirrhosis, arthritis, and tumor invasion.

Investigators at the University of Michigan (Ann Arbor, USA) worked with a strain of genetically engineered mice lacking the gene for MT1-MMP. Results published in the April 15, 2005 issue of Genes & Development revealed that MT1-MMP helped transmit the biochemical signal generated by PDGF-beta to direct mural cell growth in the microvasculature. MT1-MMP-null mice were found to have severely compromised vascular architecture, with irregularly sized vessels and weakened vessel walls.

Senior author Dr. Stephen J. Weiss, professor of internal medicine and oncology at the University of Michigan, said, "These findings, coupled with complementary reports from our group that cancer cells themselves use MT1-MMP to regulate their proliferative and metastatic properties, suggest that therapeutics directed against this single target could prove efficacious in controlling the ability of tumors to recruit new blood vessels, grow, and spread to distant sites.”



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