RESUMO
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 ß (PDGFRß) - 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 PDGFRß were examined. RESULTS: Most meningiomas displayed no KDR protein expression but elevated PDGFRß levels. Exogenous VEGFA stimulation significantly increased cell proliferation. The PDGFRß inhibition before stimulation with VEGFA abolished the proliferative stimuli. The VEGFA induced concentration-dependent PDGFRß tyrosine phosphorylation comparable to PDGFB-induced PDGFRß tyrosine phosphorylation. The PDGFRß inhibitors gambogic acid, sunitinib, and tandutinib equally impaired the migration of meningioma cells. In addition, gambogic acid suppressed the VEGFA-induced PDGFRß tyrosine phosphorylation. CONCLUSION: Collectively, our data suggest that VEGFA primarily regulates VEGF-mediated migration through PDGFRß in meningiomas. The inhibitory effect of gambogic acid and tandutinib against meningioma growth in vitro suggests that selective PDGFRß inhibitors, in combination with VEGF inhibitors, should be evaluated further as potential therapies for recurrent and malignant meningiomas.
