Glucocorticoid receptor function possibly modulates cell-cell interactions in osteoblastic metastases on rat skeleton

We analysed the glucocorticoid receptor (GR) function and its ability to modulate cell-cell interactions between the PA-m rat prostate cancer and UMR 106 osteoblast-like rat osteosarcoma cells as an in vitro model for studying GR function in PA-III cell-induced tumor and blastic reaction in rat bone, Intact GR was detected by ligand binding assays, DNA band-shift, and GR trans-activation analysis of PA-III and UMR 106 cells transiently transfected with the mouse mammary tumor, virus thymidine kinase-chloramphenicol acetyltransferase reporter gene, Dexamethasone and transforming growth factor beta 1 (TGF beta 1) inhibited the growth of PA-III and UMR 106 cells, Dexamethasone's inhibition of PA-III and UMR 106 cells was reversed by anti-TGF beta 1 antibody and exogenous insulin-like growth factor I (IGF-I), Exogenous IGF-I, urokinase-type plasminogen activator (uPA), UMR 106 conditioned media (CM) and PA-III CM stimulated the proliferation of PA-III and UMR 106 cells, The mitogenic activity exerted by uPA and PA-III CM in UMR 106 cells was completely neutralized by anti-IGF-I specific antibody, In addition, dexamethasone up-regulated TGF beta 1 mRNA and do,vn-regulated uPA mRNA expression in PA-III cells without affecting TGF beta 1 and uPA mRNA expression in UMR 106 cells, These data suggested that TGF beta 1, uPA, and IGF-I mediate at least in part cell-cell interactions and GR function in PA-III prostate cancer and UMR 106 osteosarcoma cells.