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

人前列腺癌的生长依赖于雄激素，对雄激素消融治疗有较好的疗效。但大多数接受雄激素消融治疗的前列腺癌会重新生长，并经常转移到骨骼。我们建立了SCID小鼠模型，发现肿瘤间质中巨噬细胞的侵袭影响了前列腺癌的生长。为了证实肿瘤侵袭巨噬细胞在抗雄激素治疗下对前列腺癌生长的影响，我们将雄激素依赖的人前列腺癌细胞株(LNCaP)与人巨噬细胞共移植到SCID小鼠皮下组织中。异种移植3个月后，卵巢切除小鼠LNCaP细胞的生长受到完全抑制，而与人巨噬细胞共培养的LNCaP细胞在异种移植后3个月仍可观察到。这是第一个使用雄激素依赖细胞系建立雄激素非依赖性前列腺癌模型的动物模型。提示巨噬细胞在抗雄激素治疗中对雄激素依赖型前列腺癌的生存起着重要作用。代表这一动物模型的体外模型正在进行中，以分析其潜在的机制。

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.