Transforming growth factor-beta-induced mitogenesis of human bone cancer cells

We report for the first time the bifunctional effects of transforming growth factor-beta on the growth of cloned human osteosarcoma cells (Htb96). Cell growth was assessed by determining the cell number, replication index and [3H]-thymidine incorporation following 48 hours incubation of cultured Htb96 cells with the peptide. Exposure of cells to concentrations of TGF-beta upto 40 pM caused a mitogenic response, concentrations between 40 and 800 pM failed to stimulate cell growth and higher doses caused an inhibition of cell proliferation. The initial cell density was found to alter the responsiveness of Htb96 cells to TGF-beta; stimulation of proliferation was less profound at high and low cell densities. The observed cell density- and growth factor concentration-dependent effects of TGF-beta on the growth of tumour cells might suggest the existence of an autocrine regulatory mechanism. Furthermore, by demonstrating a sensitivity to inhibition by indomethacin, we conclude that the proliferative effect of TGF-beta is at least, in part, dependent on the de novo synthesis of prostaglandins.