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This Article Full Text Full Text (PDF) All Versions of this Article: ERC-08-0219v1 16/2/415    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ishii, K. Articles by Sugimura, Y. Search for Related Content PubMed PubMed Citation Articles by Ishii, K. Articles by Sugimura, Y.

Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
¹ Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan

(Correspondence should be addressed to K Ishii; Email: kenishii{at}clin.medic.mie-u.ac.jp)

Activation of tumor–stromal interactions is considered to play a critical role in the promotion of tumorigenesis. To discover new therapeutic targets for hormone-refractory prostate tumor growth under androgen ablation therapy, androgen-sensitive LNCaP cells and the derived sublines, E9 (androgen-low-sensitive), and AIDL (androgen-insensitive), were recombined with androgen-dependent embryonic rat urogenital sinus mesenchyme (UGM). Tumors of E9+UGM and AIDL+UGM were approximately three times as large as those of LNCaP+UGM. Tumors grown in castrated hosts exhibited reduced growth as compared with those in intact hosts. However, in castrated hosts, E9+UGM and AIDL+UGM tumors were still approximately twice as large as those of LNCaP+UGM. Cell proliferation in tumors of E9+UGM and AIDL+UGM grown in castrated host, was significantly higher than that in tumors of LNCaP+UGM. In vitro, expression of fibroblast growth factor (FGF)-2 and IGF-I, but not FGF-7 mRNA, was significantly reduced in UGM under androgen starvation. In cell culture, E9 cells were responsive to FGF-2 and FGF-7 stimulation, while AIDL responded to FGF-7 and IGF-1. Expression of FGFR1 and FGFR2 was considerably higher in E9 than those in LNCaP, similarly expression of FGFR2 and IGF-IR were elevated in AIDL. These data suggest that activation of prostate cancer cell growth through growth factor receptor expression may result in the activity of otherwise androgen-independent stromal growth factor signals such as FGF-7 under conditions of androgen ablation.