Selective inhibition of MMP-14 inhibits tumor growth, invasion, and angiogenesis

1148 MMP-14 is a membrane-bound zinc-endopeptidase that drives the pericellular proteolysis that leads to tumor cell invasion. It does this directly by degrading ECM components and activating zymogens such as proMMP-2. DX-2400 is a potent and selective antibody inhibitor of MMP-14 that we have used to examine the contribution of this protease to tumor growth. This antibody displays potent anti-invasive and anti-angiogenic activity in vitro and inhibits the proliferation and angiogenesis of human tumors in preclinical models, decreasing their metastatic spread. Our studies have pharmacologically validated the role of MMP-14 in tumor growth and demonstrate the potential of a selective MMP-14 inhibitor for the treatment of solid tumors.