Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 289, Issue 5, Pages 1082-1087Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/bbrc.2001.6129
Keywords
prostate cancer; prostate-specific antigen; human adult bone; osteoplastic change; transforming growth factor-beta; autonomous mechanism; alpha(1)-antichymotrypsin
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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. (C) 2001 Elsevier Science.
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