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Cancer Research 67, 1757-1768, February 15, 2007. doi: 10.1158/0008-5472.CAN-06-3700
© 2007 American Association for Cancer Research

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Experimental Therapeutics, Molecular Targets, and Chemical Biology

Gene Alterations Identified by Expression Profiling in Tumor-Associated Endothelial Cells from Invasive Ovarian Carcinoma

Chunhua Lu1, Tomas Bonome3, Yang Li1, Aparna A. Kamat1, Liz Y. Han1, Rosemarie Schmandt1, Robert L. Coleman1, David M. Gershenson1, Robert B. Jaffe4, Michael J. Birrer3 and Anil K. Sood1,2

Departments of 1 Gynecologic Oncology and 2 Cancer Biology, University of Texas M. D. Anderson Cancer Center, Houston, Texas; 3 Cell and Cancer Biology Branch, National Cancer Institute, Bethesda, Maryland; and 4 Center for Reproductive Sciences, University of California, San Francisco, San Francisco, California

Requests for reprints: Anil K. Sood, Department of Gynecologic Oncology, University of Texas M. D. Anderson Cancer Center, Unit 1362, 1155 Herman Pressler, Houston, TX 77030. Phone: 713-745-5266; Fax: 713-792-7586; E-mail: asood{at}mdanderson.org.

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. [Cancer Res 2007;67(4):1757–68]




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2007 by the American Association for Cancer Research.