Regulation of keratinocyte integrins by scatter factor

Integrins are an important family of cell adhesion molecules which mediate cell-cell and cell-matrix interactions. Regulation of integrins has been shown to be a key step in modulating cell behaviour. Scatter factor (SF) is a paracrine growth factor which may regulate integrin expression and function. SF has been shown to be involved in many cellular processes including embryogenesis, wound healing and tumour invasion. The purpose of this study was to determine the role of SF in regulating integrin expression and function on normal human keratinocytes (NHK). The role of SF on the tyrosine phosphorylation of focal adhesion kinase (FAK), a protein participating in integrin signalling, was also investigated. A series of squamous cell carcinoma cell lines, expressing different levels of fibronectin receptor, was also used to examine the role of SF on specific integrins in mediating migration towards fibronectin. The effects of SF on the integrin expression was examined in two in vitro models: monolayer culture and histotypic culture. In monolayer culture, SF modulated integrin expression by organising surface distribution without changes in the levels of surface integrin expression. In histotypic culture, however, SF down- regulated all surface integrins examined. Integrin function was investigated by measuring the ability of NHK to adhere and migrate on various matrix proteins. SF reduced the adhesion of NHK to collagen type I, IV, laminin 1, 5 and fibronectin. SF selectively induced the migration of NHK towards fibronectin, but not to collagen type I and laminin 1. The α5β1 integrin was the main integrin which is responsible for the increase in migration. SF was able to promote the migration in all squamous cell carcinoma cell lines, confirming that the α5β1 integrin plays a significant role in SF-induced migration. SF increased the level of tyrosine phosphorylation of FAK protein in NHK after 30 minutes. These results demonstrated that there is an interrelationship between SF and integrins in NHK and that SF can modulate the behaviour of keratinocytes by modifying integrin function