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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

  1. Author:
    Kimura, T.
    Kuwata, T.
    Ashimine, S.
    Yamazaki, M.
    Yamauchi, C.
    Nagai, K.
    Ikehara, A.
    Feng, Y.
    Dimitrov, D. S.
    Saito, S.
    Ochiai, A.

  2. Author Address

    [Kimura, Taichi; Kuwata, Takeshi; Ashimine, Satoshi; Yamazaki, Manabu; Yamauchi, Chisako; Ochiai, Atsushi] East Hosp, Natl Canc Ctr, Res Ctr Innovat Oncol, Div Pathol, Chiba 2778577, Japan. [Nagai, Kanji] East Hosp, Natl Canc Ctr, Div Thorac Oncol, Chiba 2778577, Japan. [Kimura, Taichi; Ashimine, Satoshi; Ikehara, Akashi; Saito, Seiichi] Univ Ryukyus, Fac Med, Dept Organ Oriented Med, Div Urol, Okinawa, Japan. [Feng, Yang; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, Ctr Canc Res, NIH, Frederick, MD 21701 USA.;Ochiai, A, East Hosp, Natl Canc Ctr, Res Ctr Innovat Oncol, Div Pathol, 6-5-1 Kashiwanoha, Chiba 2778577, Japan.;aochiai@east.ncc.go.jp
    1. Year: 2010
    2. Date: Jan
  2. Journal: Clinical Cancer Research
    1. 16
    2. 1
    3. Pages: 121-129
  4. Type of Article: Article
  5. ISSN: 1078-0432
  1. Abstract:

    Purpose: 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. Experimental Design: 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. Clin Cancer Res; 16(1); 121-9. (C)2010 AACR.

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External Sources

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  2. DOI: 10.1158/1078-0432.ccr-09-0982
  3. View record in Web of Science®
  4. WOS: 000278404500013

Library Notes

  1. Fiscal Year: FY2009-2010
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