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The bisphosphonate YM529 inhibits osteoblastic bone tumor proliferation of prostate cancer
Author(s) -
Yonou Hiroyuki,
Ochiai Atsushi,
Ashimine Satoshi,
Maeda Hiroyuki,
Horiguchi Yutaka,
Yoshioka Kunihiko,
Ogawa Yoshihide,
Hatano Tadashi,
Tachibana Masaaki
Publication year - 2007
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.20592
Subject(s) - prostate cancer , medicine , bisphosphonate , bone metastasis , prostate , metastasis , zoledronic acid , cancer , lncap , pathology , tumor progression , bone resorption , cancer research , osteoporosis
Abstract BACKGROUND In men, prostate cancer frequently metastasizes to the bones, where it forms osteoblastic lesions with an osteolytic element that cause pain. However, the role of osteoclastogenesis in bone metastasis of human prostate cancer is unknown. Bisphosphonates are already known to be beneficical for treating osteolytic bone metastases, so we employed a model of osteoblastic bone tumor of human prostate cancer to investigate whether a new bisphosphonate (YM529: minodronate) could inhibit both the formation of bone tumors and the progression of established osteoblastic tumors. METHODS Human prostate cancer cells (LNCaP) were injected into adult human bone implants in nonobese diabetic/severe combined immunodeficient mice, after which osteoblastic bone tumors developed. YM529 (1 µg/day) was administered subcutaneously every day for 2 weeks, starting either immediately or 2 weeks after implantation of the tumor cells, and the mice were sacrificed at 4 weeks after implantation. The bone tumors were examined histologically and the number of tartrate‐resistant acid phosphatase‐stained osteoclasts in each tumor focus was counted. RESULTS Histomorphometric analysis revealed that YM529 markedly inhibited both the formation of bone tumors and the progression of established tumors, as well as markedly reducing the number of osteoclasts. CONCLUSIONS YM529 reduced the tumor burden in bone by inhibiting both the formation of new lesions and the progression of existing tumors, suggesting that osteoclasts are involved in the formation of bone tumors by prostate cancer. Treatment with this bisphosphonate may potentially be beneficial for patients with bone metastases of prostate cancer. Prostate 67: 999–1009, 2007. © 2007 Wiley‐Liss, Inc.