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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00103

FGFR1 expression and role in migration in low and high grade paediatric gliomas

 Anke Bruning-Richardson1*,  Naomi Egbivwue2, Julia V. Cockle1, Matthew Humphries3,  Azzam Ismail1, Filomena Esteves1, Claire Taylor1, Katherine Karakoula4, Ruth Ruth1,  Tracy Warr4 and  Susan Short1
  • 1University of Leeds, United Kingdom
  • 2School of Medicine, Faculty of Medicine and Health, University of Leeds, United Kingdom
  • 3Queen's University Belfast, United Kingdom
  • 4University of Wolverhampton, United Kingdom

The heterogeneous and invasive nature of paediatric gliomas poses significant treatment challenges, highlighting the importance of identifying novel chemotherapeutic targets. Recently, recurrent Fibroblast growth factor receptor 1 (FGFR1) mutations in paediatric gliomas have been reported. Here, we explored clinical relevance of FGFR1 expression, cell migration in low and high grade paediatric 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 in 3D spheroids in five rare patient-derived paediatric 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, tumour location and tumour grade among astrocytomas. Membranous pFGFR1 was associated with malignancy and tumour 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 paediatric gliomas

Keywords: Glioma, FGFR1, Migration, Immunohistochemistry, inhibitor

Received: 05 Oct 2018; Accepted: 04 Feb 2019.

Edited by:

Rimas J. Orentas, Seattle Children's Research Institute, United States

Reviewed by:

Joseph L. Lasky, Cure 4 The Kids, United States
Anshu Malhotra, Emory University, United States  

Copyright: © 2019 Bruning-Richardson, Egbivwue, Cockle, Humphries, Ismail, Esteves, Taylor, Karakoula, Ruth, Warr and Short. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Anke Bruning-Richardson, University of Leeds, Leeds, United Kingdom, A.Bruning-Richardson@hud.ac.uk