title: Identification of novel targets for antiangiogenic therapy by comparing the gene expressions of tumor and normal endothelial cells.
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.
authors.affiliation: Drug Discovery II, DSP Cancer Institute, Dainippon Sumitomo Pharma Co., Ltd, Osaka, Japan.
authors.forename: Tsuguteru
authors.initials: T
authors.lastname: Otsubo
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hida
authors.forename: Noritaka
authors.initials: N
authors.lastname: Ohga
authors.forename: Hideshi
authors.initials: H
authors.lastname: Sato
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kai
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuki
authors.forename: Hideo
authors.initials: H
authors.lastname: Takasu
authors.forename: Kosuke
authors.initials: K
authors.lastname: Akiyama
authors.forename: Nako
authors.initials: N
authors.lastname: Maishi
authors.forename: Taisuke
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Nobuo
authors.initials: N
authors.lastname: Shinohara
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nonomura
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hida
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000098:blood supply; D045744:Cell Line, Tumor; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C473249:Def6 protein, mouse; C552366:Tmem176B protein, mouse
keywords: Antiangiogenic therapy; normal endothelial cell; tumor angiogenesis; tumor endothelial cell; tumor endothelial cell marker