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Biochem Biophys Res Commun. 2001 Dec 21;289(5):1082-7.

Prostate-specific antigen induces osteoplastic changes by an autonomous mechanism.

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  • 1Pathology 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.

Abstract

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.

[PubMed - indexed for MEDLINE]
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