SPATIAL DISTRIBUTION AND FUNCTIONAL RELEVANCE OF FGFR1 AND FGFR2 EXPRESSION FOR GLIOBLASTOMA TUMOUR INVASION

Abstract

Abstract AIMS Glioblastoma (GBM) is the most common brain tumour in adults. The GBM microenvironment is made up of heterogeneous GBM cell populations, but how microenvironmental signalling pathways contribute to GBM het- erogeneity and specific GBM pathological features remains incompletely understood. Here, we compare expression of fibroblast growth factor receptors (FGFRs) within the tumour core and the invasion front, specifically investigating the functional relevance of FGFR1 and FGFR2 for in GBM invasion in vitro and in vivo. METHOD Quantification of the relative expression levels of FGFR1 and FGFR2 was determined in GBM primary patient- derived cell lines and xenograft models. Additional transcriptional profiling using RNA sequencing identified potential gene-regulatory networks involved in FGFR1-driven GBM tumour invasion. RESULTS We found FGFR1 distributed across the tumour mass and expressed in invasive GBM cells, while FGFR2 expression is confined to the tumour mass only. Loss of FGFR1, but not FGFR2, significantly reduced cell migration in vitro and tumour invasion in human GBM xenografts. Comparative analysis of RNA-sequencing data of FGFR1 and FGFR2 knockdown GBM cells revealed a FGFR1-specific gene regulatory network associated with tumour invasion. CONCLUSIONS Differential expression of FGFR1 and FGFR2 on invasive GBM cells identified FGFR1 is functionally relevant for tumour invasion in GBM. New gene candidates linked to FGFR1-mediated GBM invasion have been revealed and warrant further investigation to identify how FGFR1 regulates GBM invasion.