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

Cancer Sci. 2014 May;105(5):560-7. doi: 10.1111/cas.12394. Epub 2014 Apr 19.

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.

Keywords: Antiangiogenic therapy; normal endothelial cell; tumor angiogenesis; tumor endothelial cell; tumor endothelial cell marker.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Guanine Nucleotide Exchange Factors
  • 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

Substances

  • Angiogenesis Inhibitors
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Guanine Nucleotide Exchange Factors
  • Membrane Proteins
  • Nuclear Proteins
  • RNA, Small Interfering
  • SLAT protein, mouse
  • Tmem176B protein, mouse