Modulatory effects of interferon-γ on the fibronectin receptor function of squamous cell carcinoma cells in vitro

Abstract

We previously showed that the in vivo invasion of a squamous cell carcinoma induced by the intradermal injection of tumor cells was significantly delayed after the IFN-γ-producing gene transfer to tumor cells. With respect to the mechanism of the delayed invasion, it was suggested that the IFN-γ might inhibit the adhesion of the cells to extracellular matrices (ECM) and the subsequent locomotion. Thus, we examined the effect of IFN-γ on the adhesion of Pam-T cells to ECM. The attachment of Pam-T cells to fibronectin (FN) was significantly higher than that to laminin (LN), collagen type I (COL I) or collagen type IV (COL IV) substrata. The attachment of FN was significantly enhanced specifically by the IFN-γ-treatment of the cells, although the attachment to LN, COL I or COL IV was not altered by IFN-γ. Neither IFN-α nor IFN-β had any effect on the attachment of Pam-T cells to FN. When Pam-T cells were treated with IFN-γ together with a neutralizable anti-IFN-γ antibody, this enhancement was completely abolished. Moreover, the attachment of IFN-γ-treated Pam-T cells as well as non-treated cells to FN was blocked by the synthetic peptide Arg-Gly-Asp-Ser (RGDS), but not by the control peptide Arg-Gly-Glu-Ser. Based on these results, we conclude that IFN-γ specifically enhances the adhesiveness of Pam-T cells to FN substrata by the modulation of integrin activity.