Retinoids inhibit adhesion to laminin in human pancreatic carcinoma cells via the alpha(6)beta(1)-integrin receptor

Background & Aims: The initial step in tumor invasion and metastasis is determined by adhesion of tumor cells to basement membranes. To evaluate their potential therapeutic use in controlling local growth and metastasis, the effects of retinoids on the adhesive properties in the human pancreatic carcinoma cell line DAN-G were examined. Methods: The effects of retinoids on cellular adhesion were assessed by adhesion assays in vitro. The expression of laminin-binding proteins was characterized by Northern blotting, radioimmunoprecipitation, and flow-cytometric analysis. Results: Treatment with retinoids results in a time- and dose-dependent inhibition of DAN-G cell adhesion to fibronection and laminin but not to collagens I, IV, and VI. The adhesion of DAN-G cells to laminin could be blocked completely by anti-alpha(6) and anti-beta(1) antibodies but not by the synthetic peptide YIGSR. Flow-cytometric analysis of DAN-G cells showed no quantitative difference for alpha(6)-integrin expression in retinoid treated and untreated DAN-G cells. Furthermore, radioimmunoprecipitation showed no difference in the appearence of alpha(6) beta(1)-integrin expression after retinoid incubation. Conclusions: Retinoids decrease pancreatic carcinoma cell adhesion to laminin via an as yet unidentified mechanism involving alteration of the alpha(6) beta(1)-integrin receptor function and thereby open interesting perspectives for the modulation of infiltrative growth and metastasis in pancreatic cancer.