Targeting of bone-derived insulin-like growth factor-II by a human neutralizing antibody suppresses the growth of prostate cancer cells in a human bone environment.
OBJECTIVE
Advanced prostate cancer frequently involves the bone, where the insulin-like growth factor (IGF)-II is abundant. However, the importance of IGF-II in bone metastasis from prostate cancer is uncertain. The present study was aimed at examining the therapeutic importance of targeting IGF-II in bone metastases from prostate cancer.


METHODS
We investigated whether inhibiting IGF-II using a human neutralizing antibody (m610) suppresses the growth of prostate cancer cells in a human bone environment. Human MDA PCa 2b prostate cancer cells were inoculated into human adult bone implanted into mammary fat pad of nonobese diabetic/severe combined immunodeficient mice or inoculated into mammary fat pad of the mice without human bone implantation. The mice were treated with m610 or a control antibody (m102.4) once weekly for 4 weeks immediately after inoculation with MDA PCa 2b cells.


RESULTS
Histomorphologic examination indicated that m610 treatment significantly decreased the MDA PCa 2b tumor area in the human bone compared with the control. Ki-67 immunostaining revealed that the percentage of proliferating cancer cells in the m610-treated bone tumor sections was significantly lower than that in the control. m610 had no effect on MDA PCa 2b tumor growth in the absence of implanted human bone. m610 prevented the in vitro IGF-II-induced proliferation of MDA PCa 2b cells.


CONCLUSIONS
Our results indicate that IGF-II plays an important role in the prostate cancer cell growth in human bone, suggesting that targeting it by neutralizing antibodies offers a new therapeutic strategy for bone metastasis from prostate cancer.
Kimura
Taichi
T
Pathology Division, Research Center for Innovative Oncology, Chiba, Japan.
Kuwata
Takeshi
T
Ashimine
Satoshi
S
Yamazaki
Manabu
M
Yamauchi
Chisako
C
Nagai
Kanji
K
Ikehara
Akashi
A
Feng
Yang
Y
Dimitrov
Dimiter S
DS
Saito
Seiichi
S
Ochiai
Atsushi
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000517:prevention & control*; D001842:Bone and Bones / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000502:physiology*; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D007335:Insulin-Like Growth Factor II