Androgen receptors expressed by prostatic stromal cells obtained from younger versus older males exhibit opposite roles in prostate cancer progression.
Androgen receptors expressed by prostatic stromal cells obtained from younger versus older males exhibit opposite roles in prostate cancer progression.
复制标题
DOI：
10.1038/aja.2013.45
复制
发表时间：
2013-06
影响因子：
2.9
通讯作者：
Youyi Lu;Bo Jiang;Fu-jun Zhao;D. Cui;Qi Jiang;Jun-jie Yu;En-Hui Li;Xiaohai Wang;B. Han;S. Xia
中科院分区：
文献类型：
--
作者：
Youyi Lu;Bo Jiang;Fu-jun Zhao;D. Cui;Qi Jiang;Jun-jie Yu;En-Hui Li;Xiaohai Wang;B. Han;S. Xia
衰老是前列腺癌（PCa）的主要危险因素，前列腺基质细胞也可能促进前列腺癌的进展。因此，基质细胞对老年男性和年轻男性前列腺癌的促进作用并不相同。因此，老年男性和年轻男性前列腺基质细胞中雄激素受体（ARs）的表达也可能在前列腺癌的进展中发挥不同的作用。通过基因敲低技术和共培养系统，我们发现敲低年轻男性前列腺基质细胞中的AR可促进体外共培养PC3/LNCaP细胞的侵袭性和转移。相比之下，当LNCaP细胞与老年男性前列腺基质细胞共培养时，当AR表达下调时，LNCaP细胞的侵袭性和转移性受到抑制。此外，用小发夹RNA （small hairpin RNA, shRNA）靶向AR表达后，基质金属蛋白酶（matrix metalloproteinase， MMP）在基质细胞中的表达在年轻组中升高，而在老年组中下降或保持不变。然而，MMP9有一个例外。在体内，在抑制前列腺基质细胞中的AR表达后，观察到转移性淋巴结的发生率在年轻组中增加，但在老年组中下降。总之，这些数据表明前列腺基质细胞中的AR在老年男性和年轻男性的前列腺癌转移中起相反的作用。因此，总的来说，前列腺基质细胞中AR的功能似乎随着年龄的增长而改变，这可能是老年男性前列腺癌发病率增加的原因。
Aging is a major risk factor for prostate cancer (PCa), and prostatic stromal cells may also promote PCa progression. Accordingly, stromal cells do not equally promote PCa in older males and younger males. Therefore, it is also possible that the expression of androgen receptors (ARs) by prostatic stromal cells in older versus younger males plays different roles in PCa progression. Using a gene knockdown technique and coculture system, we found that the knockdown of the AR in prostatic stromal cells obtained from younger males could promote the invasiveness and metastasis of cocultured PC3/LNCaP cells in vitro. By contrast, the invasiveness and metastasis of LNCaP cells was inhibited when cocultured with prostatic stromal cells from older males that when AR expression was knocked down. Moreover, after targeting AR expression with small hairpin RNA (shRNA), matrix metalloproteinase (MMP) expression in stromal cells was observed to increase in the younger group, but decreased or remained unchanged in the older group. One exception, however, was observed with MMP9. In vivo, after knocking down AR expression in prostatic stromal cells, the incidence of metastatic lymph nodes was observed to increase in the younger age group, but decreased in the older age group. Together, these data suggest that the AR in prostatic stromal cells played opposite roles in PCa metastasis for older versus younger males. Therefore, collectively, the function of the AR in prostatic stromal cells appears to change with age, and this may account for the increased incidence of PCa in older males.