PMID- 10928998 OWN - NLM STAT- MEDLINE DCOM- 20000825 LR - 20191210 IS - 0892-6638 (Print) IS - 0892-6638 (Linking) VI - 14 IP - 11 DP - 2000 Aug TI - HGF/scatter factor selectively promotes cell invasion by increasing integrin avidity. PG - 1629-40 AB - Hepatocyte growth factor/scatter factor (HGF/SF) controls a genetic program known as 'invasive growth', which involves as critical steps cell adhesion, migration, and trespassing of basement membranes. We show here that in MDA-MB-231 carcinoma cells, these steps are elicited by HGF/SF but not by epidermal growth factor (EGF). Neither factor substantially alters the production or activity of extracellular matrix proteases. HGF/SF, but not EGF, selectively promotes cell adhesion on laminins 1 and 5, fibronectin, and vitronectin through a PI3-K-dependent mechanism. Increased adhesion is followed by enhanced invasiveness through isolated matrix proteins as well as through reconstituted basement membranes. Inhibition assays using function-blocking antibodies show that this phenomenon is mediated by multiple integrins including beta1, beta3, beta4, and beta5. HGF/SF triggers clustering of all these integrins at actin-rich adhesive sites and lamellipodia but does not quantitatively modify their membrane expression. These data suggest that HGF/SF promotes cell adhesion and invasiveness by increasing the avidity of integrins for their specific ligands. FAU - Trusolino, L AU - Trusolino L AD - Institute for Cancer Research and Treatment, University of Torino Medical School, 10060 Candiolo-Torino, Italy. cboccaccio@ircc.unito.it FAU - Cavassa, S AU - Cavassa S FAU - Angelini, P AU - Angelini P FAU - Ando, M AU - Ando M FAU - Bertotti, A AU - Bertotti A FAU - Comoglio, P M AU - Comoglio PM FAU - Boccaccio, C AU - Boccaccio C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (Actins) RN - 0 (Antibodies) RN - 0 (Cadherins) RN - 0 (Drug Combinations) RN - 0 (Extracellular Matrix Proteins) RN - 0 (Integrins) RN - 0 (Laminin) RN - 0 (Ligands) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Proteoglycans) RN - 119978-18-6 (matrigel) RN - 62229-50-9 (Epidermal Growth Factor) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 9007-34-5 (Collagen) RN - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Actins/drug effects/metabolism MH - Antibodies/immunology/pharmacology MH - Basement Membrane/chemistry/metabolism MH - Breast Neoplasms/enzymology/*metabolism/*pathology MH - Cadherins/metabolism MH - Cell Adhesion/drug effects MH - Cell Division/drug effects MH - Cell Movement/*drug effects MH - Collagen/metabolism MH - Cytoskeleton/drug effects/metabolism MH - Dose-Response Relationship, Drug MH - Drug Combinations MH - Epidermal Growth Factor/pharmacology MH - Extracellular Matrix Proteins/metabolism MH - Gene Expression/drug effects MH - Hepatocyte Growth Factor/*pharmacology MH - Humans MH - Integrins/antagonists & inhibitors/immunology/*metabolism MH - Laminin/metabolism MH - Ligands MH - Matrix Metalloproteinase 9/metabolism MH - Neoplasm Invasiveness/pathology MH - Phenotype MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Proteoglycans/metabolism MH - Tumor Cells, Cultured MH - Urokinase-Type Plasminogen Activator/metabolism EDAT- 2000/08/06 11:00 MHDA- 2000/09/02 11:01 CRDT- 2000/08/06 11:00 PHST- 2000/08/06 11:00 [pubmed] PHST- 2000/09/02 11:01 [medline] PHST- 2000/08/06 11:00 [entrez] AID - 10.1096/fj.14.11.1629 [doi] PST - ppublish SO - FASEB J. 2000 Aug;14(11):1629-40. doi: 10.1096/fj.14.11.1629.