HGF/scatter factor selectively promotes cell invasion by increasing integrin avidity

• Published in: The FASEB journal 2000-08, Vol.14 (11), p.1629-1640
• Main Authors: Trusolino, L, Cavassa, S, Angelini, P, Andó, M, Bertotti, A, Comoglio, P M, Boccaccio, C
• Format: Article
• Language: English
• Subjects: Actins - drug effects; Actins - metabolism; Antibodies - immunology; Antibodies - pharmacology; Basement Membrane - chemistry; Basement Membrane - metabolism; Breast Neoplasms - enzymology; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cadherins - metabolism; Cell Adhesion - drug effects; Cell Division - drug effects; Cell Movement - drug effects; Collagen - metabolism; Cytoskeleton - drug effects; Cytoskeleton - metabolism; Dose-Response Relationship, Drug; Drug Combinations; Epidermal Growth Factor - pharmacology; Extracellular Matrix Proteins - metabolism; Gene Expression - drug effects; Hepatocyte Growth Factor - pharmacology; Humans; Integrins - antagonists & inhibitors; Integrins - immunology; Integrins - metabolism; Laminin - metabolism; Ligands; Matrix Metalloproteinase 9 - metabolism; Neoplasm Invasiveness - pathology; Phenotype; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Proteoglycans - metabolism; Tumor Cells, Cultured; Urokinase-Type Plasminogen Activator - metabolism
• ISSN: 0892-6638; 1530-6860; 1530-6860
• DOI: 10.1096/fj.14.11.1629

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.