title: Delta-like ligand 4 (Dll4) predicts the prognosis of clear cell renal cell carcinoma, and anti-Dll4 suppresses tumor growth in vivo.
abstract: 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.
authors: Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai, China.
authors: Guang-Hui
authors: GH
authors: Hu
authors: Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai, China.
authors: Huan
authors: H
authors: Liu
authors: Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai, China.
authors: Peng
authors: P
authors: Lai
authors: Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai, China.
authors: Zhui-Feng
authors: ZF
authors: Guo
authors: Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai, China.
authors: Liang
authors: L
authors: Xu
authors: Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai, China.
authors: Xu-Dong
authors: XD
authors: Yao
authors: Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai, China.
authors: Jun-Hua
authors: JH
authors: Zheng
authors: Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai, China.
authors: Min
authors: M
authors: Liu
authors: Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai, China.
authors: Yun-Fei
authors: YF
authors: Xu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D016016:Proportional Hazards Models; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D012307:Risk Factors; D013997:Time Factors; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; C424126:DLL4 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering
keywords: Angiogenesis; Delta-like ligand 4; anti-Dll4; clear cell renal cell carcinoma; prognosis; tumor growth