Elucidation of the mechanisms for the growth of androgen-dependent prostate cancer in bone under anti-androgen therapy.

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Growth of human prostate cancer is dependent on androgen and responds the androgen ablation therapy effectively. But most of the prostate cancers treated by the androgen ablation therapy re-grow and frequently metastasize to the bone. We have established a SCID mice model and found that the growth of prostate cancer was affected by the infiltration of macrophages into cancer stroma .To confirm the effect of tumor infiltrating macrophages on the prostate cancer growth under anti-androgen therapy, co-xenotransplantation of androgen-dependent human prostate cancer cell line (LNCap) and human macrophages in the subcutaneous tissue of SCID mice. Though the growth of LNCap cells in ochytectomized mice was totally suppressed, that of LNCap cells with human macrophages in orchytectomized mice was observed at 3 months after xenotransplantation. This is the first animal model for androgen-independent prostate cancer model using androgen dependent cell line. The present results indicated that the infiltration of human macrophages play a critical role on the survival of androgen dependent human prostate cancer under anti-androgen therapy. In vitro model representing this animal model is now undergoing for analyzing underlying mechanism.