Document Detail


Autocrine VEGF-A/KDR loop protects epithelial ovarian carcinoma cells from anoikis.
MedLine Citation:
PMID:  19004006     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Epithelial ovarian carcinoma (EOC) patients are usually diagnosed at an advanced stage, characterized by interperitoneal carcinomatosis and production of large volumes of ascites. Vascular endothelial growth factor-A (VEGF-A) and its main signaling receptor VEGFR2 (KDR) are coexpressed in primary ovarian tumors, ascitic cells and metastases, suggesting the existence of an autocrine VEGF-A/KDR loop in EOC cells. In the present study, we examined this possibility and explored the role of this autocrine loop in protecting EOC cells from apoptosis under anchorage free growth conditions (anoikis). We found that 3 different EOC cell lines (Caov3, OVCAR3, SKOV3) express both VEGF-A and its receptors, including KDR. In these cells, KDR is constitutively phosphorylated and is detected both in the cell plasma membrane and in the nucleus. Treating EOC cells with specific internal inhibitors of KDR kinase activity or a VEGF-A neutralizing antibody abolished KDR autophosphorylation and resulted in significant increase in apoptosis when cells were grown in single-cell, anchorage-free conditions. By contrast, these blocking reagents had no effect on cell viability when EOC cells were grown in adhesive monolayers. In summary, our results indicate that an autocrine VEGF-A/KDR loop exists in EOC cells and that it plays a role in protecting the cells from anoikis. Our results imply that treating EOC patients with VEGF blocking agents may potentially reduce peritoneal dissemination by decreasing vascular permeability as well as inducing apoptosis of shed ovarian cancer cells in ascites.
Authors:
Ifat Sher; Sirin A Adham; James Petrik; Brenda L Coomber
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  124     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2008-11-27     Completed Date:  2008-12-30     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  553-61     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2008 Wiley-Liss, Inc.
Affiliation:
Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
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MeSH Terms
Descriptor/Qualifier:
Anoikis / physiology*
Autocrine Communication / drug effects,  physiology*
Blotting, Western
Cell Line, Tumor
Enzyme Inhibitors / pharmacology
Enzyme-Linked Immunosorbent Assay
Epithelial Cells / drug effects,  metabolism,  pathology
Female
Fluorescent Antibody Technique
Humans
Immunoprecipitation
In Situ Nick-End Labeling
Neoplasms, Glandular and Epithelial / metabolism*,  pathology
Ovarian Neoplasms / metabolism*,  pathology
RNA, Messenger / analysis
Vascular Endothelial Growth Factor A / drug effects,  metabolism*
Vascular Endothelial Growth Factor Receptor-2 / drug effects,  metabolism*
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/RNA, Messenger; 0/Vascular Endothelial Growth Factor A; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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