雌激素通过上调间质细胞基质金属蛋白酶2的表达促进前列腺癌的侵袭行为

ccumulating evidence suggests an enhancing effect of estrogens on prostate cancer progression. Matrix metalloproteinase 2 (MMP2), which plays an important role in prostate cancer invasion, is mainly expressed in prostatic stromal cells. Here we show that estrogen estradiol (E2) treatment upregulates MMP2 production in prostatic stromal cells, which promotes prostate cancer cell invasion in a paracrine manner. Conditioned medium (CM) was collected from estradiol (E2)-treated prostatic stromal cell line WPMY-1. The CM of E2-treated WPMY-1promoted invasion of prostate cancer (PCa) cells, as measured by Matrigel transwell assays. Treatment with E2 and PPT, an estrogen receptor-alpha (ERα) specific agonist, significantly upregulated MMP2 expression in WPMY-1 cells at both mRNA and protein levels. The CM treated with an anti-MMP2 antibody lost the stimulatory effect on invasion of PCa cells. The invasion of PCa cells were stimulated by elevated MMP2 expression induced by E2 in a paracrine manner. Our data show that estrogen estradiol induces MMP2 expression in WPMY-1 and PrSC cells. The effect of estrogen estradiol on invasion of prostate cancer cells is mediated by upregulation of MMP2 in a paracrine mechanism.