In vivo effects of the human type I insulin-like growth factor receptor antibody A12 on androgen-dependent and androgen-independent xenograft human prostate tumors

Jennifer D. Wu*, Austin Odman, Lily M. Higgins, Kathy Haugk, Robert Vessella, Dale L. Ludwig, Stephen R. Plymate

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

138 Scopus citations

Abstract

Purpose: The type I insulin-like growth factor receptor (IGF-IR) and its ligands have been shown to play a critical role in prostate carcinoma development, growth, and metastasis. Targeting the IGF-IR may be a potential treatment for prostate cancer. A fully human monoclonal antibody, A12, specific to IGF-IR, has shown potent antitumor effects in breast, colon, and pancreatic cancers in vitro and in vivo. In this study, we tested the in vivo effects of A12 on androgen-dependent and androgen-independent prostate tumor growth. Experimental Design: Androgen-dependent LuCaP 35 and androgen-independent LuCaP 35V prostate tumors were implanted s.c. into intact and castrated severe combined immunodeficient mice, respectively. When tumor volume reached about 150 to 200 mm3, A12 was injected at 40 mg/kg body weight thrice a week for up to 5 weeks. Results: We find that A12 significantly inhibits growth of androgen-dependent LuCaP 35 and androgen-independent LuCaP 35V prostate xenografts, however, by different mechanisms. In LuCaP 35 xenografts, A12 treatment induces tumor cell apoptosis or G1 cycle arrest. In LuCaP 35V xenografts, A12 treatment induces tumor cell G2-M cycle arrest. Moreover, we find that blocking the function of IGF-IR down-regulates androgen-regulated gene expression in androgen-independent LuCaP 35V tumor cells. Conclusions: Our findings suggest that A12 is a therapeutic candidate for both androgen-dependent and androgen-independent prostate cancer. Our findings also suggest an IGF-IR - dependent activity of the androgen receptor in androgen-independent prostate cancer cells.

Original languageEnglish (US)
Pages (from-to)3065-3074
Number of pages10
JournalClinical Cancer Research
Volume11
Issue number8
DOIs
StatePublished - Apr 15 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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