The bisphosphonate YM529 inhibits osteoblastic bone tumor proliferation of prostate cancer.
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 microg/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.
Yonou
Hiroyuki
H
Department of Urology, Tokyo Medical University, Tokyo, Japan. yonou428@tokyo-med.ac.jp
Ochiai
Atsushi
A
Ashimine
Satoshi
S
Maeda
Hiroyuki
H
Horiguchi
Yutaka
Y
Yoshioka
Kunihiko
K
Ogawa
Yoshihide
Y
Hatano
Tadashi
T
Tachibana
Masaaki
M
D000818:Animals; D001859:Bone Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D004164:Diphosphonates / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D014183:Transplantation, Heterologous
D004164:Diphosphonates; D007093:Imidazoles; C087958:YM 529