Gene alterations identified by expression profiling in tumor-associated endothelial cells from invasive ovarian carcinoma

Academic Article

Abstract

  • Therapeutic strategies based on antiangiogenic approaches are beginning to show great promise in clinical studies. However, full realization of these approaches requires identification of key differences in gene expression between endothelial cells from tumors versus their normal counterparts. Here, we examined gene expression differences in purified endothelial cells from 10 invasive epithelial ovarian cancers and 5 normal ovaries using Affymetrix U133 Plus 2.0 microarrays. More than 400 differentially expressed genes were identified in tumor-associated endothelial cells. We selected and validated 23 genes that were overexpressed by 3.6- to 168-fold using real-time reverse transcription-PCR and/or immunohistochemistry. Among these, the polycomb group protein enhancer of Zeste homologue 2 (EZH2), the Notch ligand Jagged1, and PTK2 were elevated 3- to 4.3-fold in tumor-associated endothelial cells. Silencing these genes individually with small interfering RNA blocked endothelial cell migration and tube formation in vitro. The present study shows that tumor and normal endothelium differ at the molecular level, which may have significant implications for the development of antiangiogenic therapies. ©2007 American Association for Cancer Research.
  • Published In

  • Cancer Research  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 13535164
  • Author List

  • Lu C; Bonome T; Li Y; Kamat AA; Han LY; Schmandt R; Coleman RL; Gershenson DM; Jaffe RB; Birrer MJ
  • Start Page

  • 1757
  • End Page

  • 1768
  • Volume

  • 67
  • Issue

  • 4