Reference - Detail
|Author||Otsubo T, Hida Y, Ohga N, Sato H, Kai T, Matsuki Y, Takasu H, Akiyama K, Maishi N, Kawamoto T, Shinohara N, Nonomura K, Hida K.|
|Title||Identification of novel targets for antiangiogenic therapy by comparing the gene expressions of tumor and normal endothelial cells.|
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.
|MeSH||Angiogenesis Inhibitors / therapeutic use* Animals Biomarkers, Tumor / genetics* Carcinoma, Renal Cell / blood supply Cell Line, Tumor Cell Movement DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Endothelial Cells / drug effects Endothelial Cells / metabolism Endothelial Cells / pathology Endothelium, Vascular / metabolism Endothelium, Vascular / pathology* Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Male Membrane Proteins / genetics Membrane Proteins / metabolism Mice Mice, Nude Middle Aged Neoplasm Transplantation Neovascularization, Pathologic / drug therapy* Neovascularization, Pathologic / genetics* Nuclear Proteins / genetics Nuclear Proteins / metabolism Oligonucleotide Array Sequence Analysis RNA Interference RNA, Small Interfering Reverse Transcriptase Polymerase Chain Reaction Up-Regulation|
|Human and Animal Cells|