Osteoblast conditioned media contain TGF-β1 and modulate the migration of prostate tumor cells and their interactions with extracellular matrix components
✍ Scribed by Claudio Festuccia; Mauro Bologna; Giovanni Luca Gravina; Fulvio Guerra; Adriano Angelucci; Ida Villanova; Danilo Millimaggi; Anna Teti
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 171 KB
- Volume
- 81
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Prostate cancers (PRCAs) frequently metastasize to bone. We show here that this process is facilitated by osteoblastmediated tumor cell recruitment. Transforming growth factor-1 (TGF-1) is produced by osteoblasts in a latent form and is activated by proteases in a cell-dependent manner. This cytokine exhibits pleiotropic effects on cell-extracellular matrix (ECM) interactions and may influence tumor cell invasion and metastasis. Our purpose was to identify the potential molecular mechanisms involved in osteoblastmediated cell recruitment and to characterize the effect of TGF-1 on adhesion, motility and invasiveness of a human prostate cancer cell line with high bone metastatic potential (PC3 cell line) in vitro. Conditioned media from osteoblast cultures (OB CM) enhanced PC3 cell chemotaxis and invasion of reconstituted basement membrane. These effects were blocked by a neutralyzing TGF-1 polyclonal antibody but not by elution of the OB CM in agarose-heparin columns, suggesting that TGF-1, but not EGF-like proteins, contribute to PC3 cell recruitment. In addition, TGF-1 directly induced chemotaxis and invasion of PC3 cells in a dosedependent manner. The TGF-1-mediated invasion and motility were accompanied by increased PC3 cell adhesion, spreading and ␣21 and ␣31 integrin expression. These events are involved in the cell adhesion to several components of basement membrane and ECM and in the selective invasion of metastatic tumor cells. Our results suggest that TGF-1 can influence cellular recognition of ECM components by prostatic cancer cells and can modulate cell adhesion and invasion leading to increased invasive potential. Given the widespread tissue distribution of TGF-1, and the high levels present in the bone, this cytokine may be an important autocrine-paracrine modulator of the bone invasive phenotype in vivo.