NDLI: Disruption of matrix metalloproteinase 2 binding to integrin alpha vbeta 3 by an organic molecule inhibits angiogenesis and tumor growth in vivo.

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Disruption of matrix metalloproteinase 2 binding to integrin alpha vbeta 3 by an organic molecule inhibits angiogenesis and tumor growth in vivo.

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Disruption of matrix metalloproteinase 2 binding to integrin alpha vbeta 3 by an organic molecule inhibits angiogenesis and tumor growth in vivo.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Silletti, S. Kessler, T. Cheresh, D. A. Boger, D. L. Goldberg, J.
Description	Author Affiliation: Silletti S ( Department of Immunology and Vascular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.);
Abstract	Matrix metalloproteinase 2 (MMP2) can associate with integrin alpha(v)beta3 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 alphav(v)beta3 and block alpha(v)beta3 interaction with MMP2. Although disrupting alpha(v)beta3/MMP2 complex formation, TSRI265 has no effect on alpha(v)beta3 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 alpha(v)beta(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.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	1
Volume Number	98
Language	English
Publisher	National Academy of Sciences
Publisher Date	2001-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Angiogenesis Inhibitors Pharmacology Antineoplastic Agents Matrix Metalloproteinase 2 Metabolism Oligopeptides Receptors, Vitronectin Chemistry Animals Cell Division Drug Effects Chick Embryo Chorion Blood Supply Collagen Cricetinae Endothelium, Vascular Enzymology Pathology Enzyme Activation Histocytochemistry Immunoblotting Matrix Metalloproteinase Inhibitors Melanoma Drug Therapy Neoplasm Transplantation Neovascularization, Pathologic Protein Binding Antagonists & Inhibitors Tumor Cells, Cultured Vitronectin Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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