Impact of Vessel Maturation on Antiangiogenic Therapy in Ovarian Cancer

Overview

Journal Am J Obstet Gynecol

Publisher Elsevier

Specialty Gynecology & Obstetrics

Date 2008 Apr 9

PMID 18395047

Citations 21

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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The Use of Alternative Strategies for Enhanced Nanoparticle Delivery to Solid Tumors.

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Escaping Antiangiogenic Therapy: Strategies Employed by Cancer Cells.

Pinto M, Sotomayor P, Carrasco-Avino G, Corvalan A, Owen G Int J Mol Sci. 2016; 17(9).

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The ZNF304-integrin axis protects against anoikis in cancer.

Aslan B, Monroig P, Hsu M, Pena G, Rodriguez-Aguayo C, Gonzalez-Villasana V Nat Commun. 2015; 6:7351.

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Anti-vascular therapies in ovarian cancer: moving beyond anti-VEGF approaches.

Choi H, Pena G, Pradeep S, Cho M, Coleman R, Sood A Cancer Metastasis Rev. 2014; 34(1):19-40.

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