Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3

• Published in: Cell Vol. 85; no. 5; pp. 683 - 693
• Main Authors: Brooks, P C, Strömblad, S, Sanders, L C, von Schalscha, T L, Aimes, R T, Stetler-Stevenson, W G, Quigley, J P, Cheresh, D A
• Format: Journal Article
• Language: English
• Published: United States 31-05-1996
• Subjects: Animals; Cell Adhesion; Cell Membrane - metabolism; Chick Embryo; Cricetinae; Gelatinases - metabolism; Humans; Matrix Metalloproteinase 2; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Melanoma, Experimental - secondary; Metalloendopeptidases - metabolism; Neoplasm Invasiveness; Neovascularization, Pathologic; Receptors, Vitronectin - metabolism; Solubility; Tumor Cells, Cultured; Vitronectin - metabolism
• ISSN: 0092-8674
• DOI: 10.1016/S0092-8674(00)81235-0

Cellular invasion depends on cooperation between adhesive and proteolytic mechanisms. Evidence is provided that the matrix metalloproteinase MMP-2 can be localized in a proteolytically active form on the surface of invasive cells, based on its ability to bind directly integrin alpha v beta 3. MMP-2 and alpha v beta 3 were specifically colocalized on angiogenic blood vessels and melanoma cells in vivo. Expression of alpha v beta 3 on cultured melanoma cells enabled their binding to MMP-2 in a proteolytically active form, facilitating cell-mediated collagen degradation. In vitro, these proteins formed an SDS-stable complex that depended on the noncatalytic C-terminus of MMP-2, since a truncation mutant lost the ability to bind alpha v beta 3. These findings define a single cell-surface receptor that regulates both matrix degradation and motility, thereby facilitating directed cellular invasion.