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

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Abstract

We analysed the glucocorticoid receptor (GR) function and its ability to modulate cell-cell interactions between the PA-III 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 (TGFb1) inhibited the growth of PA-III and UMR 106 cells. Dexamethasone's inhibition of PA-III and UMR 106 cells was reversed by anti-TGFb1 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 TGFb1 mRNA and down-regulated uPA mRNA expression in PA-III cells without affecting TGFb1 and uPA mRNA expression in UMR 106 cells. These data suggested that TGFb1, 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.

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  1. Molecular Endocrinology Laboratory, Research Center, Centre Hospitalier de L'Universite Laval (C.H.U.L.), St Foy, Quebec, Canada

    Carlos Reyes-Moreno  & Michael Koutsilieris

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  1. Carlos Reyes-Moreno
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  2. Michael Koutsilieris
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Reyes-Moreno , C., Koutsilieris , M. Glucocorticoid receptor function possibly modulates cell-cell interactions in osteoblastic metastases on rat skeleton. Clin Exp Metastasis 15, 205–217 (1997). https://doi.org/10.1023/A:1018413229570

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