Identification of novel targets for antiangiogenic therapy by comparing the gene expressions of tumor and normal endothelial cells.
Bottom Line: Targeting tumor angiogenesis is an established strategy for cancer therapy.We identified 131 genes that were differentially upregulated in 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.
Affiliation: Drug Discovery II, DSP Cancer Institute, Dainippon Sumitomo Pharma Co., Ltd, Osaka, Japan.Show MeSH
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Mentions: To identify novel markers of tumor endothelium by comparing the gene expression patterns between mTEC and mNEC, total RNA was extracted from eight independent mTEC populations derived from three types of human tumor xenografts (three melanomas, three renal carcinomas and two oral squamous cell carcinomas) and two populations of mNEC derived from two independent samples from the dermis of nude mice. RNA was used to probe an Affymetrix GeneChip Mouse Genome 430 2.0 array to determine transcriptional profiles. We focused on transcripts that were highly expressed in the three types of mTEC compared with mNEC. We detected 180 transcripts expressed in all mTEC with levels five times higher than that in mNEC. We excluded 19 genes with no human orthologs and 30 genes that were expressed less than five times higher by any mTEC compared with mNEC using qRT-PCR (Fig.2). The DNA microarray and RT-PCR analysis of representative genes including the five novel TEC markers are shown in Table3, Figure3 and Supporting Information Table S1. The levels of expression of these genes were higher in the three types of mTEC than that in mNEC. We selected 131 genes as potential TEC markers for functional screening using siRNA-mediated gene silencing (Fig.2).
Affiliation: Drug Discovery II, DSP Cancer Institute, Dainippon Sumitomo Pharma Co., Ltd, Osaka, Japan.