Beta-2 microglobulin is mitogenic to PC-3 prostatic carcinoma cells and antagonistic to transforming growth factor beta 1 action.
Previous studies have identified a M(r) 12,000 protein in rat prostatic stromal cell-conditioned medium with growth stimulatory activity to human prostatic carcinoma cells as a direct match with beta 2-microglobulin (beta 2-m). The present study was conducted to characterize the activities of human beta 2-m directly, using commercially available, purified human beta 2-m. Beta 2-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 beta 1 (TGF-beta 1)-induced growth inhibitory actions. Beta 2-m acted to stimulate [3H]thymidine incorporation in PC-3 cells in a linear, concentration-dependent and saturable manner in serum-free medium. Beta 2-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-beta 1 and lower, beta 2-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-beta 1 concentrations were refractory to beta 2-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 beta 2-m antagonistic activity to TGF-B1 growth-induced inhibition. Beta 2-m has been shown previously to associate with hormone/growth factor receptors. Together, these data suggest that beta 2-m may play a role in modulating cell proliferation, possibly through modification of ligand/receptor kinetics. Owing to the elevation of both beta 2-m and TGF-beta 1 in many dysplastic-neoplastic conditions, beta 2-m may be relevant to mechanisms of abnormal proliferation disorders and in modulating TGF-beta 1 mechanisms of actions.
Rowley
D R
DR
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
Dang
T D
TD
McBride
L
L
Gerdes
M J
MJ
Lu
B
B
Larsen
M
M
D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D006801:Humans; D007700:Kinetics; D008297:Male; D008934:Mitogens / Q000494:pharmacology*; D011467:Prostate / Q000166:cytology / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000473:pathology*; D013268:Stimulation, Chemical; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000187:drug effects; D001613:beta 2-Microglobulin / Q000494:pharmacology*
D003470:Culture Media; D008934:Mitogens; D016212:Transforming Growth Factor beta; D001613:beta 2-Microglobulin; D014316:Tritium; D013936:Thymidine