Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3.
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.
Brooks
P C
PC
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Strömblad
S
S
Sanders
L C
LC
von Schalscha
T L
TL
Aimes
R T
RT
Stetler-Stevenson
W G
WG
Quigley
J P
JP
Cheresh
D A
DA
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
D019030:Receptors, Vitronectin; D019096:Vitronectin; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2