Original Article Delta-like ligand 4 (Dll4) predicts the prognosis of clear cell renal cell carcinoma, and anti-Dll4 suppresses tumor growth in vivo

* Equal contributors. Received February 13, 2014; Accepted February 28, 2014; Epub April 15, 2014; Published May 1, 2014 Abstract: The Delta-like ligand 4 (Dll4) and Notch signaling pathway plays a key role in embryonic vascular develop- ment 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 ob- serve 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.