Hu Guang-Hui, Liu Huan, Lai Peng, Guo Zhui-Feng, Xu Liang, Yao Xu-Dong, Zheng Jun-Hua, Liu Min, Xu Yun-Fei
Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai, China.
Int J Clin Exp Pathol. 2014 Apr 15;7(5):2143-52. eCollection 2014.
The Delta-like ligand 4 (Dll4) and Notch signaling pathway plays a key role in embryonic vascular development and tumor growth. In this study, we measured the expression of Dll4 in clear cell renal cell carcinoma (ccRCC) and explored the correlation between Dll4 and ccRCC. We used sh-Dll4 treatment in a nude mouse model to observe the effect that inhibition of the Dll4/Notch pathway had on angiogenesis and vasculogenesis. We found up-regulation of Dll4 to be closely correlated with distant metastasis and worse overall survival. Cox regression analysis showed that Dll4 might be a prognostic marker of ccRCC. Blockade of Dll4/Notch signaling inhibited tumor growth in the mouse model via anti-angiogenesis and anti-vasculogenesis effects. We concluded that Dll4 might be a novel therapeutic target for the treatment of ccRCC.
Delta样配体4（Dll4）与Notch信号通路在胚胎血管发育和肿瘤生长中起关键作用。在本研究中，我们检测了Dll4在透明细胞肾细胞癌（ccRCC）中的表达，并探讨了Dll4与ccRCC之间的相关性。我们在裸鼠模型中使用sh-Dll4处理，以观察抑制Dll4/Notch通路对血管生成和血管发生的影响。我们发现Dll4的上调与远处转移及较差的总生存率密切相关。Cox回归分析表明，Dll4可能是ccRCC的一个预后标志物。在小鼠模型中，阻断Dll4/Notch信号通过抗血管生成和抗血管发生作用抑制肿瘤生长。我们得出结论，Dll4可能是治疗ccRCC的一个新的治疗靶点。
