Vascular Endothelial Growth Factor, Hepatocyte Growth Factor/Scatter Factor, Basic Fibroblast Growth Factor, and Placenta Growth Factor in Human Meningiomas and Their Relation to Angiogenesis and Malignancy

Lamszus, Katrin; Lengler, Ulrike; Schmidt, Nils Ole; Stavrou, D.; Ergün, Süleyman; Westphal, Manfred

doi:10.1097/00006123-200004000-00033

Cited by 79 publications

(71 citation statements)

References 23 publications

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“…In contrast, Pietsch et al (1997) and Nishikawa et al (1998) could not find a relationship between VEGF expression and tumour vasculature (Pietsch et al , 1997; Nishikawa et al , 1998). Lamszuz et al (2000) noted a strong correlation between meningioma histological grade and VEGF expression, wherein increased VEGF expression was linked to higher WHO grades. However, Barresi and Tuccari (2010) showed the absence of correlation between VEGF expression and WHO grade (Barresi and Tuccari, 2010).…”

Section: Discussionmentioning

confidence: 96%

“…Several studies have demonstrated the significance of VEGF in the proliferation and migration of meningiomas in which VEGF has been upregulated (Provias and Claffey, 1997; Christov et al , 1999; Lamszuz et al , 2000; Park et al , 2000; Yamasaki, 2000). Some groups have observed a correlation between the degree of VEGF expression and tumour vascularity or invasiveness (Samoto et al , 1995; Provias and Claffey, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…Although VEGF is upregulated in meningiomas (Provias and Claffey, 1997; Christov et al , 1999; Lamszuz et al , 2000; Park et al , 2000; Yamasaki, 2000), it is unknown whether the degree of malignancy correlates with the expression of VEGF (Provias and Claffey, 1997; Lamszuz et al , 2000; Yamasaki, 2000). …”

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confidence: 99%

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

et al. 2012

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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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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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“…2,11 The extent of VEGF expression does not seem to be associated with the size of the meningioma or the degree of malignancy in humans, 10,12 but some studies contradict this conclusion. 13 In veterinary oncology, the prognostic significance of angiogenesis has been investigated for canine cutaneous mast cell tumors, 14 canine cutaneous squamous cell carcinomas, 15 canine seminomas, 16 canine mammary tumors, 17,18 and feline invasive mammary carcinomas. 19 Additionally, plasma VEGF has been investigated as a potential predictor of response to treatments such as radiation, but VEGF expression has not yet been proven to be a prognostic factor.…”

mentioning

confidence: 99%

Vascular Endothelial Growth Factor Expression in Canine Intracranial Meningiomas and Association with Patient Survival

Platt¹,

Scase²,

Adams³

et al. 2006

J Vet Int Med

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“…It was also demonstrated that intratumoral upregulation of VEGF induced a long-range attraction of transplanted human NSCs from distant sites in the adult brain 24 . In addition to VEGF, activation of MMPs has also been pointed as a mechanism of hypoxia-mediated NSC tropism to malignant areas 20,25,26 . Taken together, these data indicated that tumor-derived hypoxia-inducible chemo-attractant factors play a critical role in promoting tumor-tropic migration of NSCs.…”

Section: Introductionmentioning

confidence: 99%

MMP14 as a novel downstream target of VEGFR2 in migratory glioma-tropic neural stem cells

et al. 2015

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Neural stem cell (NSC)-based carriers have been presented as promising therapeutic tools for the treatment of infiltrative brain tumors due to their intrinsic tumor homing properties. They have demonstrated the ability to migrate towards distant tumor microsatellites and effectively deliver the therapeutic payload, thus significantly improving survival in experimental animal models for brain tumors. Despite such optimistic results, the efficacy of NSC-based anti-cancer therapy has been limited due to the restricted tumor homing ability of NSCs. To examine this issue, we investigated the mechanisms of tumor-tropic migration of an FDA-approved NSC line, HB1.F3.CD, by performing a gene expression analysis. We identified vascular endothelial growth factor-A (VEGFA) and membrane-bound matrix metalloproteinase (MMP14) as molecules whose expressions are significantly elevated in migratory NSCs. We observed increased expression of VEGF receptor 2 (VEGFR2) in the focal adhesion complexes of migratory NSCs, with downstream activation of VEGFR2-dependent kinases such as p-PLCγ, p-FAK, and p-Akt, a signaling cascade reported to be required for cellular migration. In an in vivo orthotopic glioma xenograft model, analysis of the migratory trail showed that NSCs maintained expression of VEGFR2 and preferentially migrated within the perivascular space. Knockdown of VEGFR2 via shRNAs led to significant downregulation of MMP14 expression, which resulted in inhibited tumor-tropic migration. Overall, our results suggest, for the first time, the involvement of VEGFR2-regulated MMP14 in the tumor-tropic migratory behavior of NSCs. Our data warrant investigation of MMP14 as a target for enhancing the migratory properties of NSC carriers and optimizing the delivery of therapeutic payloads to disseminated tumor burdens.

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Vascular Endothelial Growth Factor, Hepatocyte Growth Factor/Scatter Factor, Basic Fibroblast Growth Factor, and Placenta Growth Factor in Human Meningiomas and Their Relation to Angiogenesis and Malignancy

Cited by 79 publications

References 23 publications

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

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

Vascular Endothelial Growth Factor Expression in Canine Intracranial Meningiomas and Association with Patient Survival

MMP14 as a novel downstream target of VEGFR2 in migratory glioma-tropic neural stem cells

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