MITOGENIC RESPONSE OF OSTEOBLAST CELLS TO PROSTATE-SPECIFIC ANTIGEN SUGGESTS AN ACTIVATION OF LATENT TGF-BETA AND A PROTEOLYTIC MODULATION OF CELL-ADHESION RECEPTORS

During studies of mitogens in prostate, PSA quantities as low as 2.5 ng/mL caused cultured osteoblast cells to proliferate beyond controls (p=<0.05). Investigation of this novel mitogenicity suggested the use of several mechanisms by PSA, namely: 1) the activation of latent hTGF-β in PC-3 conditioned medium, PSA treated conditioned medium stimulated DNA uptake in UMR-106 cells to 78% of acid treated conditioned medium, while DNA incorporation was less than controls with anti-hTGF-β neutralizing IgG; and 2) the proteolytic modulation of cell surface receptors with temporary contact inhibition, PSA significantly stimulated cell detachment while hTGF- β enhanced cell attachment of confluent Saos-2 cells above controls. Clinically, these results suggest that PSA may provide a mechanism for both tumor spread and the osteoblastic metastasis so common to prostate cancer. © 1993 Academic Press, Inc.