Prostate-specific antigen induces osteoplastic changes by an autonomous mechanism.
The high prevalence of osteoplastic bone metastasis in prostate cancer (PC) is believed to be attributable to the production of osteoblast-stimulating factors by PC cells. Prostate-specific antigen (PSA) is a serine protease and an important serological marker for PC. Exposure of osteoblasts to PSA in vitro was found to result in cell proliferation and marked upregulation of transforming growth factor-beta (TGF-beta) mRNA expression. This PSA-induced increase in osteoblast proliferation was inhibited by anti-TGF-beta antibodies and serine protease inhibitors. In vivo, PSA markedly enhanced osteoplastic changes in human adult bone implanted into NOD/SCID mice without PC cells, and alpha(1)-antichymotrypsin prevented the PSA-induced increase in bone volume. PSA promotes osteoplastic change by activating an osteoblast autonomous mechanism that is independent of the production of bone growth factors by PC cells.
Yonou
H
H
Pathology Division, Division of Thoracic Oncology, National Cancer Center Research Institute East, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Aoyagi
Y
Y
Kanomata
N
N
Kamijo
T
T
Oda
T
T
Yokose
T
T
Hasebe
T
T
Nagai
K
K
Hatano
T
T
Ogawa
Y
Y
Ochiai
A
A
D000368:Aged; D000818:Animals; D001859:Bone Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary; D016025:Bone Transplantation; D002455:Cell Division; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D010006:Osteoblasts / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000008:administration & dosage / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D017430:Prostate-Specific Antigen