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Prostate‐specific antigen induces apoptosis of osteoclast precursors: Potential Role in osteoblastic bone metastases of prostate cancer
Author(s) -
Goya Masato,
Ishii Genichiro,
Miyamoto Shinichi,
Hasebe Takahiro,
Nagai Kanji,
Yonou Hiroyuki,
Hatano Tadashi,
Ogawa Yoshihide,
Ochiai Atsushi
Publication year - 2006
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20375
Subject(s) - osteoclast , lncap , prostate cancer , cancer research , osteoblast , bone metastasis , osteolysis , medicine , bone resorption , endocrinology , apoptosis , prostate , prostate specific antigen , cancer , chemistry , in vitro , biochemistry , receptor , surgery
BACKGROUND Prostate cancer is frequently associated with bone metastases with marked osteoblastic changes and low osteoclastic activity but its mechanism is not well understood. We previously reported that prostate‐specific antigen (PSA) stimulated the proliferation and the activation of osteoblasts. In this study, we investigated the effect of PSA on osteoclastogenesis. METHODS Two human prostate cancer cell lines and PSA were directly injected into human adult bone (HAB) implanted into NOD/SCID mice, followed by morphological analysis. RAW 264.7 cells, murine osteoclast precursor, were treated with PSA. RESULTS PSA‐producing LNCaP and PSA caused a significant decrease of osteoclast precursors and osteoclasts in HAB accompanied by osteoblast proliferation and new bone formation, while PSA‐nonproducing PC3 showed increasing osteoclasts with osteolysis. PSA induced apoptosis of RAW 264.7 cells in vitro. PSA‐induced apoptosis was dependent of enzymatic activity of PSA and was specific to immature tartrate‐resistant acid phosphatase‐negative mononuclear RAW 264.7 cells. CONCLUSIONS PSA plays a crucial role for osteoblastic bone metastasis by promoting both osteoblasts proliferation and apoptosis of osteoclast precursors. Prostate 66: 1573–1584, 2006. © 2006 Wiley‐Liss, Inc.