Modulatory effects of interferon-gamma on the fibronectin receptor function of squamous cell carcinoma cells in vitro.
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-gamma-producing gene transfer to tumor cells. With respect to the mechanism of the delayed invasion, it was suggested that the IFN-gamma might inhibit the adhesion of the cells to extracellular matrices (ECM) and the subsequent locomotion. Thus, we examined the effect of IFN-gamma 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 to FN was significantly enhanced specifically by the IFN-gamma-treatment of the cells, although the attachment to LN, COL I or COL IV was not altered by IFN-gamma. Neither IFN-alpha nor IFN-beta had any effect on the attachment of Pam-T cells to FN. When Pam-T cells were treated with IFN-gamma together with a neutralizable anti-IFN-gamma antibody, this enhancement was completely abolished. Moreover, the attachment of IFN-gamma-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-gamma specifically enhances the adhesiveness of Pam-T cells to FN substrata by the modulation of integrin activity.
Maruguchi
Y
Y
Department of Dermatology, Faculty of Medicine, Kyoto University, Japan.
Toda
K
K
Watanabe
Y
Y
Imamura
S
S
D000595:Amino Acid Sequence; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology / Q000628:therapy*; D002448:Cell Adhesion / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000187:drug effects* / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology
D009842:Oligopeptides; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; D007371:Interferon-gamma; C059453:RGES peptide; C046617:arginyl-glycyl-aspartyl-serine