Modulation of scatter factor/hepatocyte growth factor activity by cell-substratum adhesion.
Scatter factor/hepatocyte growth factor (SF/HGF) is a multifunctional growth and motility factor whose activities vary with cell type. Here, the composition of the substratum was found to profoundly alter the scattering activities of SF/HGF, but not its mitogenetic effects, in MDCK cells. Whereas enhancement of DNA synthesis and induction of cell flattening by SF/HGF were independent of substratum composition (i.e. occurred on both fibronectin and vitronectin surfaces), colony dispersion as a result of cell separation fails to occur or is markedly reduced on surfaces where vitronectin is the major adhesive ligand. Prolonged exposure of non-scattering cultures to SF/HGF resulted in cells at colony margins producing long protrusions, which indicate that the motility of these cells is stimulated but 'frustrated' by the lack of breakdown of cell-cell adhesion. Scattering therefore appears to comprise two major components: increased motility and breakdown of cell-cell adhesion. The pathway leading to the breakdown of cell-cell contacts is modulated by downstream signals from extracellular matrix receptors. When cultured on immobilised fibronectin, vitronectin or a surface containing both, colony dissociation correlates with the presence of fibronectin, suggesting that positive signals from fibronectin receptors are required for SF/HGF-induced cell separation. Comparison of the findings in this study with those of a recent report on the modulation of SF/HGF-induced tubulogenesis by ECM (Santos, O. F. P. and Nigam, S. K. (1993) Dev. Biol. 160, 293-302), where vitronectin in type-1 collagen gels alters the pattern of SF/HGF-induced MDCK tubule formation from highly branched to long and unbranched, suggests that cell motility enhancement leads to tubule formation whereas the breakdown of cell-cell adhesion is required for tubule branching.
Clark
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Department of Anatomy and Cell Biology, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, UK.
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D048429:Cell Size; D003584:Cytological Techniques; D004247:DNA / Q000096:biosynthesis; D004285:Dogs; D005353:Fibronectins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D013499:Surface Properties; D019096:Vitronectin
D005353:Fibronectins; D006023:Glycoproteins; D019096:Vitronectin; D017228:Hepatocyte Growth Factor; D004247:DNA