title: Vascular endothelial growth factor signals through platelet-derived growth factor receptor β in meningiomas in vitro.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF)-mediated angiogenesis mediates tumour growth and metastasis. Meningiomas are primarily benign, slow-growing, highly vascularised tumours. Aside from VEGF, there is little data on the function of major angiogenic proteins in meningiomas.
  
  
  METHODS
  The VEGFA, platelet-derived growth factor B (PDGFB), and their respective receptors - VEGF receptor 2 (KDR) and PDGF receptor β (PDGFRβ) - were quantified using real-time PCR and a TaqMan Protein Assay in meningiomas in vivo and in vitro. The effect of VEGFA and PDGFB on cell proliferation and the tyrosine phosphorylation of PDGFRβ were examined.
  
  
  RESULTS
  Most meningiomas displayed no KDR protein expression but elevated PDGFRβ levels. Exogenous VEGFA stimulation significantly increased cell proliferation. The PDGFRβ inhibition before stimulation with VEGFA abolished the proliferative stimuli. The VEGFA induced concentration-dependent PDGFRβ tyrosine phosphorylation comparable to PDGFB-induced PDGFRβ tyrosine phosphorylation. The PDGFRβ inhibitors gambogic acid, sunitinib, and tandutinib equally impaired the migration of meningioma cells. In addition, gambogic acid suppressed the VEGFA-induced PDGFRβ tyrosine phosphorylation.
  
  
  CONCLUSIONS
  Collectively, our data suggest that VEGFA primarily regulates VEGF-mediated migration through PDGFRβ in meningiomas. The inhibitory effect of gambogic acid and tandutinib against meningioma growth in vitro suggests that selective PDGFRβ inhibitors, in combination with VEGF inhibitors, should be evaluated further as potential therapies for recurrent and malignant meningiomas.
authors.affiliation: Department of Neurosurgery, University of Tuebingen, Hoppe-Seyler-Strasse 3, Tuebingen 72076, Germany. christina.pfister@med.uni-tuebingen.de
authors.forename: C
authors.initials: C
authors.lastname: Pfister
authors.forename: H
authors.initials: H
authors.lastname: Pfrommer
authors.forename: M S
authors.initials: MS
authors.lastname: Tatagiba
authors.forename: F
authors.initials: F
authors.lastname: Roser
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008577:Meningeal Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008579:Meningioma / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000077210:Sunitinib; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D044004:Xanthones / Q000494:pharmacology
chemical_list: D042501:Angiogenic Proteins; D007211:Indoles; D010879:Piperazines; D020574:Proto-Oncogene Proteins c-sis; D011758:Pyrroles; D011799:Quinazolines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D044004:Xanthones; D014443:Tyrosine; C052659:gambogic acid; C464670:tandutinib; D020797:Receptor, Platelet-Derived Growth Factor beta; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib