Impact of vessel maturation on antiangiogenic therapy in ovarian cancer

Am J Obstet Gynecol. 2008 Apr;198(4):477.e1-9; discussion 477.e9-10. doi: 10.1016/j.ajog.2007.12.028.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal, Humanized
  • Benzamides
  • Bevacizumab
  • Endothelial Cells / drug effects*
  • Endothelial Cells / 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


  • 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