Gene alterations identified by expression profiling in tumor-associated endothelial cells from invasive ovarian carcinoma.
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.
Lu
Chunhua
C
Departments of Gynecologic Oncology and Cancer Biology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Bonome
Tomas
T
Li
Yang
Y
Kamat
Aparna A
AA
Han
Liz Y
LY
Schmandt
Rosemarie
R
Coleman
Robert L
RL
Gershenson
David M
DM
Jaffe
Robert B
RB
Birrer
Michael J
MJ
Sood
Anil K
AK
D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000473:pathology*; D015398:Signal Transduction; D015854:Up-Regulation