Department of Gynecologic Oncology, U.T. M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Cancer Cell. 2010 Aug 9;18(2):185-97. doi: 10.1016/j.ccr.2010.06.016.
Although VEGF-targeted therapies are showing promise, new angiogenesis targets are needed to make additional gains. Here, we show that increased Zeste homolog 2 (EZH2) expression in either tumor cells or in tumor vasculature is predictive of poor clinical outcome. The increase in endothelial EZH2 is a direct result of VEGF stimulation by a paracrine circuit that promotes angiogenesis by methylating and silencing vasohibin1 (vash1). Ezh2 silencing in the tumor-associated endothelial cells inhibited angiogenesis mediated by reactivation of VASH1, and reduced ovarian cancer growth, which is further enhanced in combination with ezh2 silencing in tumor cells. Collectively, these data support the potential for targeting ezh2 as an important therapeutic approach.
虽然血管内皮生长因子（VEGF）靶向治疗显示出了前景，但仍需要新的血管生成靶点以取得更多的疗效。在这里，我们发现肿瘤细胞或肿瘤血管中 Zeste 同源物 2（EZH2）表达增加预示着不良的临床结局。内皮细胞 EZH2 的增加是血管生成的旁分泌通路通过甲基化和沉默血管抑制素 1（vash1）从而促进血管生成的直接结果。在肿瘤相关内皮细胞中沉默 Ezh2 可抑制 VASH1 再激活介导的血管生成，并减少卵巢癌的生长，而与肿瘤细胞中 Ezh2 沉默联合使用则进一步增强了这种效果。总之，这些数据支持了将 Ezh2 作为一种重要的治疗方法进行靶向治疗的潜力。
