Osteoblast conditioned media contain TGF-beta 1 and modulate the migrationof prostate tumor cells and their interactions with extracellular matrix components

prostate cancers (PRCAs) frequently metastasize to bone. We show here that this process is facilitated by osteoblast-mediated tumor cell recruitment. Transforming growth factor-beta 1 (TGF-beta 1) is produced by osteoblasts i n a latent form and is activated by proteases in a cell-dependent manner, T his cytokine exhibits pleiotropic effects on cell-extracellular matrix (ECM ) interactions and may influence tumor cell invasion and metastasis, Our pu rpose was to identify the potential molecular mechanisms involved in osteob last-mediated cell recruitment and to characterize the effect of TGF-beta 1 on adhesion, motility and invasiveness of a human prostate canter cell lin e with high bone metastatic potential (PC3 cell line) in vitro. Conditioned media from osteoblast cultures (OB CM) enhanced PC3 cell chemotaxis and in vasion of reconstituted basement membrane. These effects were blocked by a neutralyzing TGF-beta 1 polyclonal antibody but not by elution of the OB CM in agarose-heparin columns, suggesting that TGF-beta 1, but not EGF-like p roteins, contribute to PC3 cell recruitment. In addition, TGF-beta 1 direct ly induced chemotaxis and invasion of PC3 cells in a dose-dependent manner. The TGF-beta 1-mediated invasion and motility were accompanied by increase d PC3 cell adhesion, spreading and alpha 2 beta 1 and alpha 3 beta 1 integr in expression. These events are involved in the cell adhesion to several co mponents of basement membrane and ECM and in the selective invasion of meta static tumor cells. Our results suggest that TGF-beta 1 can influence cellu lar recognition of ECM components by prostatic cancer cells and can modulat e cell adhesion and invasion leading to increased invasive potential. Given the widespread tissue distribution of TGF-beta 1, and the high levels pres ent in the bone, this cytokine may be an important autocrine-paracrine modu lator of the bone invasive phenotype in vivo. (C) 1999 Wiley-Liss, Inc.