title: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Gynecologic Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Lu
authors.forename: Premal H
authors.initials: PH
authors.lastname: Thaker
authors.forename: Yvonne G
authors.initials: YG
authors.lastname: Lin
authors.forename: Whitney
authors.initials: W
authors.lastname: Spannuth
authors.forename: Charles N
authors.initials: CN
authors.lastname: Landen
authors.forename: William M
authors.initials: WM
authors.lastname: Merritt
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Jennings
authors.forename: Robert R
authors.initials: RR
authors.lastname: Langley
authors.forename: David M
authors.initials: DM
authors.lastname: Gershenson
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.forename: Lee M
authors.initials: LM
authors.lastname: Ellis
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jaffe
authors.forename: Robert L
authors.initials: RL
authors.lastname: Coleman
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D001549:Benzamides; D000068258:Bevacizumab; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D000068877:Imatinib Mesylate; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D020286:Pericytes / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001549:Benzamides; D010879:Piperazines; D020574:Proto-Oncogene Proteins c-sis; D011743:Pyrimidines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000068877:Imatinib Mesylate; D020797:Receptor, Platelet-Derived Growth Factor beta