β-2 Microglobulin Is Mitogenic to PC-3 Prostatic Carcinoma Cells and Antagonistic to Transforming Growth Factor β1 Action

Previous studies have identified a Mr 12,000 protein in rat prostatic stromal cell-conditioned medium with growth stimulatory activity to human prostatic carcinoma cells as a direct match with β2-microglobulin (β2-m). The present study was conducted to characterize the activities of human β2-m directly, using commercially available, purified human β2-m. β2-m was assayed for growth stimulatory activity to human PC-3 prostatic carcinoma cells and rat PS-1 prostatic stromal cells and for antagonistic activity to transforming growth factor β1 (TGF-β1)-induced growth inhibitory actions. β2-m acted to stimulate [3H]thymidine incorporation in PC-3 cells in a linear, concentration-dependent and saturable manner in serum-free medium. β2-m stimulated cell proliferation and significantly decreased population doubling times in both PC-3 and PS-1 cell lines. At half-maximal concentrations of TGF-β and lower, β2-m acted in a concentration-dependent, antagonistic manner, acting to stimulate growth-inhibited PC-3 cells to fully neutralize TGF-B1 activity. In contrast, cells exposed to maximum activity TGF-01 concentrations were refractory to β2-m action, regardless of the concentration tested. This represents the first report to demonstrate a growth-stimulatory activity of B2-m with carcinoma/epithelial cells and to show β2-m antagonistic activity to TGF-B1 growth-induced inhibition. β2-m has been shown previously to associate with hormone/growth factor receptors. Together, these data suggest that β2-m may play a role in modulating cell proliferation, possibly through modification of ligand/receptor kinetics. Owing to the elevation of both β2-m and TGF-01 in many dysplastic-neoplastic conditions, β2-m may be relevant to mechanisms of abnormal proliferation disorders and in modulating TGF-01 mechanisms of actions.