TRANSFORMING GROWTH-FACTOR-BETA UP-REGULATES THE INTEGRIN-MEDIATED ADHESION OF HUMAN PROSTATIC-CARCINOMA CELLS TO TYPE-I COLLAGEN

Prostate cancer frequently metastasizes to bone, and we propose that t his process may be facilitated by the adhesion of metastatic cells to bone-derived type I collagen, We examined collagen receptor function a nd regulation in osteotropic PC-3 human prostatic carcinoma cells. PC- 3 cell adhesion to immobilized human type I collagen was promoted by M n2+ and Mg2+ ions and was RGD-independent. Antibodies directed against beta 1 or alpha 2 integrin subunits inhibited adhesion to collagen by 90% and 53%, respectively, suggesting involvement of the alpha 2 beta 1 receptor, Anti-alpha 1 or anti-alpha 3 antibodies had no effect on adhesion, Flow cytometry and immunoprecipitation of [S-35]methionine-l abeled cells demonstrated that alpha 2 beta 1 was the major collagen r eceptor expressed by PC-3 cells, The pretreatment of PC-3 cells with t ransforming growth factor-beta 1 (TGF-beta 1), a major bone-derived gr owth factor, caused a rapid (2 h) 2-fold increase in the de novo synth esis of alpha 2 and beta 1 integrin subunits, and also increased by 2- to 3-fold the adhesion and spreading of PC-3 cells on collagen, We co nclude that alpha 2 beta 1 is the major collagen receptor employed by PC-3 cells, and that alpha 2 beta 1 upregulation by TGF-beta is associ ated with an increased adhesion and spreading on collagen, The data su ggest that exposure of metastatic PC-3 cells to the high levels of TGF -beta in bone may promote their ability to adhere to bone-derived coll agen, which may thereby facilitate the localization of metastatic cell s in the skeleton.