Decrease in stromal androgen receptor associates with androgen-independent disease and promotes prostate cancer cell proliferation and invasion.
Decrease in stromal androgen receptor associates with androgen-independent disease and promotes prostate cancer cell proliferation and invasion.
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DOI：
10.1111/j.1582-4934.2008.00279.x
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发表时间：
2008-12
影响因子：
5.3
通讯作者：
Lee P
中科院分区：
文献类型：
--
作者：
Li Y;Li CX;Ye H;Chen F;Melamed J;Peng Y;Liu J;Wang Z;Tsou HC;Wei J;Walden P;Garabedian MJ;Lee P
雄激素受体（AR）在前列腺的基质细胞和上皮细胞中表达。大多数关于前列腺癌中AR表达和功能的研究集中在恶性上皮细胞而不是基质细胞。在这项研究中，我们检测了雄激素依赖性和非依赖性前列腺癌中基质AR的水平，以及基质AR在前列腺癌生长和侵袭中的功能。我们发现癌组织周围的基质AR水平降低，特别是在雄激素非依赖性癌症中。使用两种端粒酶永生化的人基质细胞系，一种AR阳性，另一种AR阴性，我们证明了缺乏AR的基质细胞在体外刺激共培养的前列腺癌细胞的细胞增殖，并在裸鼠中与PC 3上皮细胞共注射时增强体内肿瘤生长。相反，表达AR的基质细胞在体外和体内抑制前列腺癌的生长。与肿瘤生长平行，体外侵袭实验显示，缺乏AR的基质细胞使PC 3细胞的侵袭能力增加一个数量级，而表达AR的基质细胞降低这种作用。这些结果表明基质AR对前列腺癌生长和侵袭具有负调节作用。这为雄激素消融治疗的失败提供了潜在的新机制见解，并且间质AR的重新激活可能是治疗激素难治性前列腺癌的新治疗方法。
Androgen receptor (AR) is expressed in both stromal and epithelial cells of the prostate. The majority of studies on AR expression and function in prostate cancer is focused on malignant epithelial cells rather than stromal cells. In this study, we examined the levels of stromal AR in androgen-dependent and -independent prostate cancer and the function of stromal AR in prostate cancer growth and invasion. We showed that stromal AR levels were decreased in the areas surrounding cancerous tissue, especially in androgen-independent cancer. Using two telomerase-immortalized human stromal cell lines, one AR-positive and the other AR-negative, we demonstrated that stromal cells lacking AR stimulated cell proliferation of co-cultured prostate cancer cells in vitro and enhanced tumour growth in vivo when co-injected with PC3 epithelial cells in nude mice. In contrast, stromal cells expressing AR suppressed prostate cancer growth in vitro and in vivo. In parallel with cancer growth, in vitro invasion assays revealed that stromal cells lacking AR increased the invasion ability of PC3 cell by one order of magnitude, while stromal cells expressing AR reduced this effect. These results indicate a negative regulation of prostate cancer growth and invasion by stromal AR. This provides potentially new mechanistic insights into the failure of androgen ablation therapy, and the reactivation of stromal AR could be a novel therapeutic approach for treating hormone refractory prostate cancer.
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影响因子：
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作者：
Castellón, E;Venegas, K;Huidobro, C
通讯作者：
Huidobro, C
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通讯作者：
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