| 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 |
Related Documents
:
|
4369426 - Utilization of ascites plasma very low density lipoprotein triglycerides by ehrlich cells. 4860576 - Autoxidation of polyunsaturated esters in water: chemical structure and biological acti... 2757796 - Investigations on the function of creatine kinase in ehrlich ascites tumor cells. 3173146 - Luminol-dependent chemiluminescence in antibody-sensitized neutrophils stimulated with ... 16931106 - Metaphase arrest and cell death induced by etoposide on hela cells. 2211496 - Trigger factor depletion or overproduction causes defective cell division but does not ... |
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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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
Previous Document: Imbalance of DNA-dependent protein kinase subunits in polycythemia vera peripheral blood stem cells.
Next Document: Genomic instability and histone H3 phosphorylation induction by the Ras-mitogen activated protein ki...