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dc.contributor.authorEgbivwie, Naomi
dc.contributor.authorCockle, Julia V.
dc.contributor.authorHumphries, Matthew
dc.contributor.authorIsmail, Azzam
dc.contributor.authorEsteves, Filomena
dc.contributor.authorTaylor, Claire
dc.contributor.authorKarakoula, Katherine
dc.contributor.authorMorton, Ruth
dc.contributor.authorWarr, Tracy
dc.contributor.authorShort, Susan C.
dc.contributor.authorBrüning-Richardson, Anke
dc.date.accessioned2019-03-14T15:41:08Z
dc.date.available2019-03-14T15:41:08Z
dc.date.issued2019-03-13
dc.identifier.issn2234-943Xen
dc.identifier.doi10.3389/fonc.2019.00103
dc.identifier.urihttp://hdl.handle.net/2436/622206
dc.description.abstractThe heterogeneous and invasive nature of pediatric gliomas poses significant treatment challenges, highlighting the importance of identifying novel chemotherapeutic targets. Recently, recurrent Fibroblast growth factor receptor 1 (FGFR1) mutations in pediatric gliomas have been reported. Here, we explored the clinical relevance of FGFR1 expression, cell migration in low and high grade pediatric gliomas and the role of FGFR1 in cell migration/invasion as a potential chemotherapeutic target. A high density tissue microarray (TMA) was used to investigate associations between FGFR1 and activated phosphorylated FGFR1 (pFGFR1) expression and various clinicopathologic parameters. Expression of FGFR1 and pFGFR1 were measured by immunofluorescence and by immunohistochemistry (IHC) in 3D spheroids in five rare patient-derived pediatric low-grade glioma (pLGG) and two established high-grade glioma (pHGG) cell lines. Two-dimensional (2D) and three-dimensional (3D) migration assays were performed for migration and inhibitor studies with three FGFR1 inhibitors. High FGFR1 expression was associated with age, malignancy, tumor location and tumor grade among astrocytomas. Membranous pFGFR1 was associated with malignancy and tumor grade. All glioma cell lines exhibited varying levels of FGFR1 and pFGFR1 expression and migratory phenotypes. There were significant anti-migratory effects on the pHGG cell lines with inhibitor treatment and anti-migratory or pro-migratory responses to FGFR1 inhibition in the pLGGs. Our findings support further research to target FGFR1 signaling in pediatric gliomas.en
dc.formatapplication/PDFen
dc.language.isoenen
dc.publisherFrontiers Mediaen
dc.relation.urlhttps://www.frontiersin.org/articles/10.3389/fonc.2019.00103/fullen
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subjectpaediatric gliomasen
dc.subjectFGFR1en
dc.subjectinvasionen
dc.subjectimmunohistochemistryen
dc.titleFGFR1 expression and role in migration in low and high grade pediatric gliomasen
dc.typeJournal article
dc.identifier.journalFrontiers in Oncologyen
dc.date.accepted2019-02-04
rioxxterms.funderUniversity of Wolverhamptonen
rioxxterms.identifier.projectUOW140319TWen
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
rioxxterms.licenseref.startdate2019-03-14en
dc.source.volume9
dc.source.issue103
dc.source.beginpage1
dc.source.endpage17
refterms.dateFCD2019-03-14T15:41:08Z
refterms.versionFCDVoR
refterms.dateFOA2019-03-14T15:41:08Z


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