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This Article Accepted manuscript (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.

K Ishii, Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, 514-8507, Japan
T Imamura, Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, Japan
K Iguchi, Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan
S Arase, Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, Japan
Y Yoshio, Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, Japan
K Arima, Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, Japan
K Hirano, Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan
Y Sugimura, Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, Japan

Correspondence: Kenichiro Ishii, Email: kenishii{at}clin.medic.mie-u.ac.jp

Abstract

In tumor microenvironments, activation of tumor-stromal interactions is considered to play a critical role in promotion of tumorigenesis. To discover new therapeutic targets for hormone-refractory prostate tumor growth under androgen ablation therapy, androgen-sensitive LNCaP and its sublines, androgen-low-sensitive E9 and androgen-insensitive AIDL, were recombined with androgen-dependent embryonic rat urogenital sinus mesenchyme (UGM) to simulate the tumor microenvironment. Tumors of E9 + UGM and AIDL + UGM were approximately three times as large as those of LNCaP + UGM. All tumors grown in castrated host reduced tumorigenesis as compared with those in intact host, whereas tumors of E9 + UGM and AIDL + UGM were still approximately twice as large as those of LNCaP + UGM. In addition, cell proliferation in tumors of E9 + UGM and AIDL + UGM grown in castrated host was significantly higher than that in tumors of LNCaP + UGM. Among typical stromal growth factors, mRNA expressions of FGF-2 and IGF-I, but not FGF-7, were significantly reduced in androgen-starved culture condition of UGM. In in vitro cell culture, E9 and/or AIDL showed high responsiveness to FGF-2, FGF-7, and IGF-I stimulation. Expressions of FGFR1, FGFR2, and IGF-IR in E9 and/or AIDL were considerably higher than those in LNCaP. These data suggest that varied activations of prostate cancer cell growth through growth factor receptor may be responsible to androgen-independent stromal growth factor signals such as FGF-7 under androgen ablation therapy.