Autocrine VEGF-A/KDR loop protects epithelial ovarian carcinoma cells from anoikis

Ifat Sher, Sirin A. Adham, James Petrik, Brenda L. Coomber

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)553-561
Number of pages9
JournalInternational Journal of Cancer
Volume124
Issue number3
DOIs
Publication statusPublished - Feb 1 2009

Fingerprint

Anoikis
Vascular Endothelial Growth Factor A
Carcinoma
Apoptosis
Ascites
Cell Membrane
Capillary Permeability
Neutralizing Antibodies
Adhesives
Ovarian Neoplasms
Cell Survival

Keywords

  • Anoikis
  • epithelial ovarian cancer
  • KDR
  • VEGF

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Autocrine VEGF-A/KDR loop protects epithelial ovarian carcinoma cells from anoikis. / Sher, Ifat; Adham, Sirin A.; Petrik, James; Coomber, Brenda L.

In: International Journal of Cancer, Vol. 124, No. 3, 01.02.2009, p. 553-561.

Research output: Contribution to journalArticle

Sher, Ifat ; Adham, Sirin A. ; Petrik, James ; Coomber, Brenda L. / Autocrine VEGF-A/KDR loop protects epithelial ovarian carcinoma cells from anoikis. In: International Journal of Cancer. 2009 ; Vol. 124, No. 3. pp. 553-561.
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