AbstractsBiology & Animal Science

Identification of Novel Targets for Antiangiogenic Therapy

by 嗣輝 大坪




Institution: Hokkaido University
Department: 歯学
Degree: 博士(歯学)
Year: 2014
Keywords: tumor endothelial cell; tumor endothelial cell marker; tumor angiogenesis; antiangiogenic therapy
Record ID: 1232066
Full text PDF: http://hdl.handle.net/2115/56321


Abstract

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