title: Mitogenic response of osteoblast cells to prostate-specific antigen suggests an activation of latent TGF-beta and a proteolytic modulation of cell adhesion receptors.
abstract: 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-beta 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-beta neutralizing IgG; and 2) the proteolytic modulation of cell surface receptors with temporary contact inhibition, PSA significantly stimulated cell detachment while hTGF-beta 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.
authors.affiliation: Department of Diagnostic Immunology Research and Biochemistry, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: C S
authors.initials: CS
authors.lastname: Killian
authors.forename: D A
authors.initials: DA
authors.lastname: Corral
authors.forename: E
authors.initials: E
authors.lastname: Kawinski
authors.forename: R I
authors.initials: RI
authors.lastname: Constantine
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002455:Cell Division; D006868:Hydrolysis; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D012516:Osteosarcoma; D010960:Plasminogen Activators / Q000494:pharmacology; D017430:Prostate-Specific Antigen / Q000494:pharmacology*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D016212:Transforming Growth Factor beta; D010960:Plasminogen Activators; D017430:Prostate-Specific Antigen