Disruption of matrix metalloproteinase 2 binding to integrin α v β 3 by an organic molecule inhibits angiogenesis and tumor growth in vivo

Matrix metalloproteinase 2 (MMP2) can associate with integrin α v β 3 on the surface of endothelial cells, thereby promoting vascular invasion. Here, we describe an organic molecule (TSRI265) selected for its ability to bind to integrin α v β 3 and block α v β 3 interaction with MMP2. Although disrupting α v β 3 /MMP2 complex formation, TSRI265 has no effect on α v β 3 binding to its extracellular matrix ligand vitronectin and does not influence MMP2 activation or catalytic activity directly. However, TSRI265 acts as a potent antiangiogenic agent and thereby blocks tumor growth in vivo . These findings suggest that activated MMP2 does not facilitate vascular invasion during angiogenesis unless it forms a complex with α v β 3 on the endothelial cell surface. By disrupting endothelial cell invasion without broadly suppressing cell adhesion or MMP function, the use of compounds such as TSRI265 may provide a novel therapeutic approach for diseases associated with uncontrolled angiogenesis.