期刊
BRITISH JOURNAL OF CANCER
卷 107, 期 10, 页码 1702-1713出版社
SPRINGERNATURE
DOI: 10.1038/bjc.2012.459
关键词
meningioma; VEGF; PDGFR beta; gambogic acid; tandutinib
类别
资金
- Else Uebelmesser-Stiftung
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 beta (PDGFR beta) - 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 PDGFR beta were examined. RESULTS: Most meningiomas displayed no KDR protein expression but elevated PDGFR beta levels. Exogenous VEGFA stimulation significantly increased cell proliferation. The PDGFR beta inhibition before stimulation with VEGFA abolished the proliferative stimuli. The VEGFA induced concentration-dependent PDGFR beta tyrosine phosphorylation comparable to PDGFB-induced PDGFR beta tyrosine phosphorylation. The PDGFR beta inhibitors gambogic acid, sunitinib, and tandutinib equally impaired the migration of meningioma cells. In addition, gambogic acid suppressed the VEGFA-induced PDGFR beta tyrosine phosphorylation. CONCLUSION: Collectively, our data suggest that VEGFA primarily regulates VEGF-mediated migration through PDGFR beta in meningiomas. The inhibitory effect of gambogic acid and tandutinib against meningioma growth in vitro suggests that selective PDGFR beta inhibitors, in combination with VEGF inhibitors, should be evaluated further as potential therapies for recurrent and malignant meningiomas. British Journal of Cancer (2012) 107, 1702-1713. doi:10.1038/bjc.2012.459 www.bjcancer.com Published online 9 October 2012 (C) 2012 Cancer Research UK
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