Control of meningioma cell growth by platelet-derived growth factor (PDGF)

Mauro, Alessandro; Sapio, Alessia Di; Mocellini, Cristina; Schiffer, Davide

doi:10.1016/0022-510x(95)00106-c

Cited by 16 publications

(10 citation statements)

References 21 publications

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“…We confirmed previous findings regarding meningioma biomarkers [3, 5, 9, 11, 12, 16, 19, 21, 28, 30, 32, 38, 39, 43–45, 48, 52, 56]. All investigated markers tested positive in all meningiomas, regardless of WHO grade.…”

Section: Discussionsupporting

confidence: 91%

“…in ovarian carcinoma [17, 53] and peritoneal metastases of colorectal carcinomas [18] targeting αvβ3-integrin or folate receptor α and VEGF-α, respectively. For the development of a similar approach in meningioma surgery, various biomarkers have been suggested, including epithelial membrane antigen (EMA), platelet-derived growth factor beta (PDGF-β), vascular endothelial growth factor A (VEGF-α), and somatostatin receptor type 2 (SSTR-2) [3, 5, 9, 11, 12, 16, 19, 21, 28, 30, 32, 38, 39, 43–45, 48, 52, 56]. However, the suitability of these markers for fluorescence-guided imaging meningioma surgery has not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

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SSTR-2 as a potential tumour-specific marker for fluorescence-guided meningioma surgery

et al. 2018

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BackgroundMeningiomas are the most frequently occurring primary intracranial tumours in adults. Surgical removal can only be curative by complete resection; however surgical access can be challenging due to anatomical localization and local invasion of bone and soft tissues. Several intraoperative techniques have been tried to improve surgical resection, including intraoperative fluorescence guided imaging; however, no meningioma-specific (fluorescent) targeting has been developed yet. Here, we aimed to identify the most promising biomarkers for targeted intra-operative fluorescence guided meningioma surgery.MethodsOne hundred forty-eight meningioma specimens representing all meningioma grades were analysed using immunohistochemistry (IHC) on tissue microarrays (TMAs) to determine expression patterns of meningioma biomarkers epithelial membrane antigen (EMA), platelet-derived growth factor β (PDGF-β), vascular endothelial growth factor α (VEGF-α), and somatostatin receptor type 2 (SSTR-2). Subsequently, the most promising biomarker was selected based on TArget Selection Criteria (TASC). Marker expression was examined by IHC in 3D cell culture models generated from freshly resected tumour material.ResultsTMA-IHC showed strongest staining for SSTR-2. All cases were positive, with 51.4% strong/diffuse, 30.4% moderate/diffuse and only 18.2% focal/weak staining patterns. All tested biomarkers showed at least weak positivity in all meningiomas, regardless of WHO grade. TASC analysis showed that SSTR-2 was the most promising target for fluorescence guided imaging, with a total score of 21 (out of 22). SSTR-2 expression was determined on original patient tumours and 3D cultures of three established cultures.ConclusionsSSTR-2 expression was highly sensitive and specific in all 148 meningiomas, regardless of WHO grade. According to TASC analysis, SSTR-2 is the most promising receptor for meningioma targeting. After establishing in vitro meningioma models, SSTR-2 cell membrane expression was confirmed in two of three meningioma cultures as well. This indicates that specific fluorescence in an experimental setting can be performed for the further development of targeted fluorescence guided meningioma surgery and near-infrared fluorescent tracers targeting SSTR-2.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

SSTR-2 as a potential tumour-specific marker for fluorescence-guided meningioma surgery

et al. 2018

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“…Previous studies looking at the expression of PDGF and it's receptor in meningiomas have demonstrated the widespread expression of these molecules in most meningiomas, 18,19 particularly the beta receptor, in meningiomas of all grades. 20 In addition there is in vitro evidence suggesting autocrine activity 21 which may be blocked with specific inhibitors. 22 Other studies have also shown a high rate of expression of IGF and its receptor, [23][24][25] and there is in vitro evidence of its functionality in meningioma cell cultures.…”

Section: Discussionmentioning

confidence: 99%

Activation of multiple growth factor signalling pathways is frequent in meningiomas

et al. 2015

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A minority of meningiomas are difficult to treat with surgery or radiotherapy, and chemotherapeutic alternatives are limited. This study aims to better understand pathways that are active in meningiomas, in order to direct future treatment strategies. We investigated the expression and activation of multiple growth factor receptors, their ligands and downstream signalling pathways in 30 meningiomas using immunohistochemistry. Expression was correlated with chromosome 22q loss. Membrane expression of VEGF receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR)β was seen in 83% of tumors, Axl in 70%, EGFR in 50% and insulin-like growth factor receptor in 47%. Expression was similar in low- and high-grade tumors, but membrane EGFR expression was not seen in tumors showing chromosome 22q loss (P < 0.05). Expression of ligands (IGF, NRG, VEGF, Gas 6), and signalling proteins (Mek, Erk, Jnk, Akt) and pS6RP, was widespread. Western blot confirmed widespread Axl expression and supported selective expression of EGFR in NF2-intact meningiomas. The majority of meningiomas express and show activation of multiple growth factor receptors and their signalling pathways, irrespective of tumor grade. In addition to previously reported receptors, Axl offers a new therapeutic target. The findings also suggest that anti-EGFR based therapies may be less effective in meningiomas with 22q loss.

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“…Yang (2001) showed that nearly all meningiomas express PDGFB and PDGFR β in vitro , and both were increased in WHO °II meningiomas. Several groups have proposed an autocrine mechanism in meningiomas, based on the co-expression of PDGFB and PDGFR β , which regulate growth (Wang et al , 1990; Figarella-Branger et al , 1994; Kuratsu et al , 1994; Mauro et al , 1995). …”

Section: Discussionmentioning

confidence: 99%

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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Control of meningioma cell growth by platelet-derived growth factor (PDGF)

Cited by 16 publications

References 21 publications

SSTR-2 as a potential tumour-specific marker for fluorescence-guided meningioma surgery

SSTR-2 as a potential tumour-specific marker for fluorescence-guided meningioma surgery

Activation of multiple growth factor signalling pathways is frequent in meningiomas

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

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