Identification of novel targets for antiangiogenic therapy by comparing the gene expressions of tumor and normal endothelial cells

Cancer Science

Tsuguteru Otsubo⁴  Yasuhiro Hida⁸  Noritaka Ohga³  Hideshi Sato¹  Toshihiro Kai⁵  Yasushi Matsuki⁶  Hideo Takasu⁷  Kosuke Akiyama³  Nako Maishi³  Taisuke Kawamoto³  Nobuo Shinohara²  Katsuya Nonomura² 

[1]Group I, Intellectual Property, Dainippon Sumitomo Pharma Co., Ltd, Osaka, Japan

[2]Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

[3]Department of Vascular Biology, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan

[4]Drug Discovery II, DSP Cancer Institute, Dainippon Sumitomo Pharma Co., Ltd, Osaka, Japan

[5]Omics Group, Genomic Science Laboratories, Drug Research Division, Dainippon Sumitomo Pharma Co., Ltd, Osaka, Japan

[6]Global Strategy Group, Global Oncology Office, Dainippon Sumitomo Pharma Co., Ltd, Osaka, Japan

[7]Drug Discovery IV, DSP Cancer Institute, Dainippon Sumitomo Pharma Co., Ltd, Osaka, Japan

[8]Department of Cardiovascular and Thoracic Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

关键词: Antiangiogenic therapy;    normal endothelial cell;    tumor angiogenesis;    tumor endothelial cell;    tumor endothelial cell marker;   

DOI  :  10.1111/cas.12394

来源: Wiley

【 摘 要 】

Abstract

Targeting tumor angiogenesis is an established strategy for cancer therapy. Because angiogenesis is not limited to pathological conditions such as cancer, molecular markers that can distinguish between physiological and pathological angiogenesis are required to develop more effective and safer approaches for cancer treatment. To identify such molecules, we determined the gene expression profiles of murine tumor endothelial cells (mTEC) and murine normal endothelial cells using DNA microarray analysis followed by quantitative reverse transcription–polymerase chain reaction analysis. We identified 131 genes that were differentially upregulated in mTEC. Functional analysis using siRNA-mediated gene silencing revealed five novel tumor endothelial cell markers that were involved in the proliferation or migration of mTEC. The expression of DEF6 and TMEM176B was upregulated in tumor vessels of human renal cell carcinoma specimens, suggesting that they are potential targets for antiangiogenic intervention for renal cell carcinoma. Comparative gene expression analysis revealed molecular differences between tumor endothelial cells and normal endothelial cells and identified novel tumor endothelial cell markers that may be exploited to target tumor angiogenesis for cancer treatment.

【 授权许可】

CC BY-NC-ND   
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.