title: Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3.
abstract: 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.
authors.affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: P C
authors.initials: PC
authors.lastname: Brooks
authors.forename: S
authors.initials: S
authors.lastname: Strömblad
authors.forename: L C
authors.initials: LC
authors.lastname: Sanders
authors.forename: T L
authors.initials: TL
authors.lastname: von Schalscha
authors.forename: R T
authors.initials: RT
authors.lastname: Aimes
authors.forename: W G
authors.initials: WG
authors.lastname: Stetler-Stevenson
authors.forename: J P
authors.initials: JP
authors.lastname: Quigley
authors.forename: D A
authors.initials: DA
authors.lastname: Cheresh
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D002642:Chick Embryo; D006224:Cricetinae; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D020778:Matrix Metalloproteinase 2; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D008666:Metalloendopeptidases / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D019030:Receptors, Vitronectin / Q000378:metabolism*; D012995:Solubility; D014407:Tumor Cells, Cultured; D019096:Vitronectin / Q000378:metabolism
chemical_list: D019030:Receptors, Vitronectin; D019096:Vitronectin; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2