Impact of vessel maturation on antiangiogenic therapy in ovarian cancer.

Abstract

OBJECTIVE:

The purpose of this study was to examine the functional and therapeutic significance of pericytes in ovarian cancer vasculature.

STUDY DESIGN:

Tumor vessel morphologic condition and efficacy of endothelial and pericyte targeting were examined with the use of in vivo ovarian cancer models. The expression of platelet-derived growth factor (PDGF) ligands and receptors was examined in endothelial, pericyte-like, and ovarian cancer cells.

RESULTS:

Relative to normal vessels, tumor vasculature was characterized by loosely attached pericytes in reduced density. PDGF-BB was expressed predominantly by the endothelial and cancer cells, whereas PDGFRbeta was present in pericyte-like cells. PDGF-BB significantly increased the migration of and VEGF production by pericyte-like cells; PDGFRbeta blockade abrogated these effects. Dual VEGF (VEGF-Trap) and PDGF-B (PDGF-Trap) targeted therapy was more effective in inhibiting in vivo tumor growth than either agent alone.

CONCLUSION:

Aberrations in the tumor microenvironment contribute to endothelial cell survival. Strategies that target both endothelial cells and pericytes should be considered for clinical trials.

• Authors: Chunhua Lu, Premal H Thaker, Yvonne G Lin, Whitney Spannuth, Charles N Landen, William M Merritt, Nicholas B Jennings, Robert R Langley, David M Gershenson, George D Yancopoulos, Lee M Ellis, Robert B Jaffe, Robert L Coleman, Anil K Sood
• Journal: American journal of obstetrics and gynecology (Am J Obstet Gynecol) Vol. 198 Issue 4 Pg. 477.e1-9; discussion 477.e9-10 (Apr 2008) ISSN: 1097-6868 [Electronic] United States
• PMID: 18395047 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Benzamides
• Piperazines
• Proto-Oncogene Proteins c-sis
• Pyrimidines
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Bevacizumab
• Imatinib Mesylate
• Receptor, Platelet-Derived Growth Factor beta

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Antibodies, Monoclonal (pharmacology)
• Antibodies, Monoclonal, Humanized
• Benzamides
• Bevacizumab
• Endothelial Cells (drug effects, metabolism)
• Female
• Gene Expression (drug effects)
• Imatinib Mesylate
• Mice
• Neovascularization, Pathologic (drug therapy)
• Ovarian Neoplasms (metabolism)
• Pericytes (metabolism)
• Piperazines (pharmacology)
• Proto-Oncogene Proteins c-sis (metabolism)
• Pyrimidines (pharmacology)
• Receptor, Platelet-Derived Growth Factor beta (drug effects)
• Reverse Transcriptase Polymerase Chain Reaction
• Vascular Endothelial Growth Factor A (metabolism)