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Vascular endothelial growth factor signals through platelet-derived growth factor receptor β in meningiomas in vitro

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:...

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Autores principales: Pfister, C, Pfrommer, H, Tatagiba, M S, Roser, F
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493872/
https://www.ncbi.nlm.nih.gov/pubmed/23047550
http://dx.doi.org/10.1038/bjc.2012.459
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author Pfister, C
Pfrommer, H
Tatagiba, M S
Roser, F
author_facet Pfister, C
Pfrommer, H
Tatagiba, M S
Roser, F
author_sort Pfister, C
collection PubMed
description 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. CONCLUSION: 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.
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spelling pubmed-34938722013-11-06 Vascular endothelial growth factor signals through platelet-derived growth factor receptor β in meningiomas in vitro Pfister, C Pfrommer, H Tatagiba, M S Roser, F Br J Cancer Translational Therapeutics 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. CONCLUSION: 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. Nature Publishing Group 2012-11-06 2012-10-09 /pmc/articles/PMC3493872/ /pubmed/23047550 http://dx.doi.org/10.1038/bjc.2012.459 Text en Copyright © 2012 Cancer Research UK https://creativecommons.org/licenses/by-nc-sa/3.0/From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Translational Therapeutics
Pfister, C
Pfrommer, H
Tatagiba, M S
Roser, F
Vascular endothelial growth factor signals through platelet-derived growth factor receptor β in meningiomas in vitro
title Vascular endothelial growth factor signals through platelet-derived growth factor receptor β in meningiomas in vitro
title_full Vascular endothelial growth factor signals through platelet-derived growth factor receptor β in meningiomas in vitro
title_fullStr Vascular endothelial growth factor signals through platelet-derived growth factor receptor β in meningiomas in vitro
title_full_unstemmed Vascular endothelial growth factor signals through platelet-derived growth factor receptor β in meningiomas in vitro
title_short Vascular endothelial growth factor signals through platelet-derived growth factor receptor β in meningiomas in vitro
title_sort vascular endothelial growth factor signals through platelet-derived growth factor receptor β in meningiomas in vitro
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493872/
https://www.ncbi.nlm.nih.gov/pubmed/23047550
http://dx.doi.org/10.1038/bjc.2012.459
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