Scatter factor regulation of integrin expression and function on oral epithelial cells

Integrin receptors and the growth factor, scatter factor (SF; also known as hepatocyte growth factor) have been shown to modulate similar cellular processes including embryogenesis, wound healing and tumour invasion. The purpose of this study was to examine the role of SF in the regulation of integrin expression, migration and adhesion in normal human oral keratinocytes (NHK). Integrin expression was examined using flow cytometry, SF did not alter levels of expression but had a dramatic effect on cell morphology, inducing migratory filopodia and lamellipodia. SF selectively induced migration towards fibronectin, but not towards collagen I. Integrin function was further investigated by measuring the ability of NHK to adhere and migrate on various integrin ligands. SF reduced adhesion of NHK to collagen types I and IV, laminins 1 and 5 and fibronectin. The inclusion of function-blocking antibodies revealed that SF mediated upregulation of migration through α₅β₁ integrin and downregulation of adhesion through α_v integrins. SF increased tyrosine phosphorylation of FAK protein in NHK after a 30-min treatment. These results show that SF can affect keratinocyte behaviour by modifying integrin function but not expression.