A role for FGFR1 in paediatric gliomas

Naomi Egbivwie, Tracy Warr, Matthew Humphries, Filomena Esteves, Susan C Short, Julia V. Cockle, Anke Bruning-Richardson

Research output: Contribution to journalMeeting Abstract

Abstract

INTRODUCTION
Paediatric high-grade gliomas (pHGGs) are highly invasive tumours associated with extremely poor prognosis. There is urgent clinical need to develop novel therapeutic strategies that can target the process of tumour migration and invasion. Fibroblast growth factor receptors (FGFRs) are transmembrane receptor tyrosine kinases associated with glioma tumourigenesis that play a role in regulating cell migration and invasion. An increased frequency of FGFR1 mutations has recently been described in paediatric gliomas (Zhang et al. 2013). Here, the role of FGFR1 in paediatric gliomas was investigated.

METHOD AND MATERIALS
FGFR1 levels (phosphorylated/unphosphorylated) and cellular localisation were determined by immunofluorescence in two pHGG cell lines (KNS42 and SF188) and five short-term cultures derived from pilocytic astrocytomas (grade 1). FGFR1 activity was stimulated by addition of FGF2. The activity of three FGFR1 inhibitors on cell migration after stimulation was assessed by live cell imaging and in a 3D spheroid invasion assay. FGFR1 levels in low and high-grade paediatric and adult tumour types were investigated in a commercial tissue microarray (TMA).

RESULTS
FGFR1 was found to be expressed among all cell lines examined by immunofluorescence. Phosphorylated (activated) FGFR1 was elevated in some cell lines after stimulation with FGF2. Live cell imaging of inhibitor-treated cells and spheroid invasion assays suggest pro-migratory effects of FGFR1 inhibition in low-grade versus anti-migratory in high-grade tumours. High FGFR1 expression in astrocytomas from patients aged under 18 compared to the 18–60 age group (χ2 = 11.578, p = 0.0031) was determined in the TMA sample set. There was a significant association of high FGFR1 levels with grade 2 and 3 astrocytomas.

DISCUSSION
We report the presence of FGFR1 among low and high-grade paediatric gliomas and a role in cell migration after stimulation with ligand. Treatment with FGFR1 inhibitors may elicit a different effect on cell migration depending on tumour grade.
Original languageEnglish
Pages (from-to)24
Number of pages1
JournalNeuro-Oncology
DOIs
Publication statusPublished - Jan 2018
Externally publishedYes
EventBritish Neuro Oncology Society Conference: Enhancing Science, Enhancing Survival - Edinburgh, United Kingdom
Duration: 21 Jun 201723 Jun 2017
https://www.bnos.org.uk/wp-content/uploads/2017/08/BNOS-2017-Conference-Report.pdf (Link to Conference Report)

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Glioma
Cell Movement
Pediatrics
Astrocytoma
Fibroblast Growth Factor 2
Neoplasms
Cell Line
Fluorescent Antibody Technique
Fibroblast Growth Factor Receptors
Receptor Protein-Tyrosine Kinases
Mutation Rate
Age Groups
Ligands
Therapeutics

Cite this

Egbivwie, N., Warr, T., Humphries, M., Esteves, F., Short, S. C., Cockle, J. V., & Bruning-Richardson, A. (2018). A role for FGFR1 in paediatric gliomas. Neuro-Oncology, 24. https://doi.org/10.1093/neuonc/nox.238.108
Egbivwie, Naomi ; Warr, Tracy ; Humphries, Matthew ; Esteves, Filomena ; Short, Susan C ; Cockle, Julia V. ; Bruning-Richardson, Anke. / A role for FGFR1 in paediatric gliomas. In: Neuro-Oncology. 2018 ; pp. 24.
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abstract = "INTRODUCTIONPaediatric high-grade gliomas (pHGGs) are highly invasive tumours associated with extremely poor prognosis. There is urgent clinical need to develop novel therapeutic strategies that can target the process of tumour migration and invasion. Fibroblast growth factor receptors (FGFRs) are transmembrane receptor tyrosine kinases associated with glioma tumourigenesis that play a role in regulating cell migration and invasion. An increased frequency of FGFR1 mutations has recently been described in paediatric gliomas (Zhang et al. 2013). Here, the role of FGFR1 in paediatric gliomas was investigated.METHOD AND MATERIALSFGFR1 levels (phosphorylated/unphosphorylated) and cellular localisation were determined by immunofluorescence in two pHGG cell lines (KNS42 and SF188) and five short-term cultures derived from pilocytic astrocytomas (grade 1). FGFR1 activity was stimulated by addition of FGF2. The activity of three FGFR1 inhibitors on cell migration after stimulation was assessed by live cell imaging and in a 3D spheroid invasion assay. FGFR1 levels in low and high-grade paediatric and adult tumour types were investigated in a commercial tissue microarray (TMA).RESULTSFGFR1 was found to be expressed among all cell lines examined by immunofluorescence. Phosphorylated (activated) FGFR1 was elevated in some cell lines after stimulation with FGF2. Live cell imaging of inhibitor-treated cells and spheroid invasion assays suggest pro-migratory effects of FGFR1 inhibition in low-grade versus anti-migratory in high-grade tumours. High FGFR1 expression in astrocytomas from patients aged under 18 compared to the 18–60 age group (χ2 = 11.578, p = 0.0031) was determined in the TMA sample set. There was a significant association of high FGFR1 levels with grade 2 and 3 astrocytomas.DISCUSSIONWe report the presence of FGFR1 among low and high-grade paediatric gliomas and a role in cell migration after stimulation with ligand. Treatment with FGFR1 inhibitors may elicit a different effect on cell migration depending on tumour grade.",
author = "Naomi Egbivwie and Tracy Warr and Matthew Humphries and Filomena Esteves and Short, {Susan C} and Cockle, {Julia V.} and Anke Bruning-Richardson",
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Egbivwie, N, Warr, T, Humphries, M, Esteves, F, Short, SC, Cockle, JV & Bruning-Richardson, A 2018, 'A role for FGFR1 in paediatric gliomas', Neuro-Oncology, pp. 24. https://doi.org/10.1093/neuonc/nox.238.108

A role for FGFR1 in paediatric gliomas. / Egbivwie, Naomi; Warr, Tracy; Humphries, Matthew; Esteves, Filomena; Short, Susan C; Cockle, Julia V.; Bruning-Richardson, Anke.

In: Neuro-Oncology, 01.2018, p. 24.

Research output: Contribution to journalMeeting Abstract

TY - JOUR

T1 - A role for FGFR1 in paediatric gliomas

AU - Egbivwie, Naomi

AU - Warr, Tracy

AU - Humphries, Matthew

AU - Esteves, Filomena

AU - Short, Susan C

AU - Cockle, Julia V.

AU - Bruning-Richardson, Anke

PY - 2018/1

Y1 - 2018/1

N2 - INTRODUCTIONPaediatric high-grade gliomas (pHGGs) are highly invasive tumours associated with extremely poor prognosis. There is urgent clinical need to develop novel therapeutic strategies that can target the process of tumour migration and invasion. Fibroblast growth factor receptors (FGFRs) are transmembrane receptor tyrosine kinases associated with glioma tumourigenesis that play a role in regulating cell migration and invasion. An increased frequency of FGFR1 mutations has recently been described in paediatric gliomas (Zhang et al. 2013). Here, the role of FGFR1 in paediatric gliomas was investigated.METHOD AND MATERIALSFGFR1 levels (phosphorylated/unphosphorylated) and cellular localisation were determined by immunofluorescence in two pHGG cell lines (KNS42 and SF188) and five short-term cultures derived from pilocytic astrocytomas (grade 1). FGFR1 activity was stimulated by addition of FGF2. The activity of three FGFR1 inhibitors on cell migration after stimulation was assessed by live cell imaging and in a 3D spheroid invasion assay. FGFR1 levels in low and high-grade paediatric and adult tumour types were investigated in a commercial tissue microarray (TMA).RESULTSFGFR1 was found to be expressed among all cell lines examined by immunofluorescence. Phosphorylated (activated) FGFR1 was elevated in some cell lines after stimulation with FGF2. Live cell imaging of inhibitor-treated cells and spheroid invasion assays suggest pro-migratory effects of FGFR1 inhibition in low-grade versus anti-migratory in high-grade tumours. High FGFR1 expression in astrocytomas from patients aged under 18 compared to the 18–60 age group (χ2 = 11.578, p = 0.0031) was determined in the TMA sample set. There was a significant association of high FGFR1 levels with grade 2 and 3 astrocytomas.DISCUSSIONWe report the presence of FGFR1 among low and high-grade paediatric gliomas and a role in cell migration after stimulation with ligand. Treatment with FGFR1 inhibitors may elicit a different effect on cell migration depending on tumour grade.

AB - INTRODUCTIONPaediatric high-grade gliomas (pHGGs) are highly invasive tumours associated with extremely poor prognosis. There is urgent clinical need to develop novel therapeutic strategies that can target the process of tumour migration and invasion. Fibroblast growth factor receptors (FGFRs) are transmembrane receptor tyrosine kinases associated with glioma tumourigenesis that play a role in regulating cell migration and invasion. An increased frequency of FGFR1 mutations has recently been described in paediatric gliomas (Zhang et al. 2013). Here, the role of FGFR1 in paediatric gliomas was investigated.METHOD AND MATERIALSFGFR1 levels (phosphorylated/unphosphorylated) and cellular localisation were determined by immunofluorescence in two pHGG cell lines (KNS42 and SF188) and five short-term cultures derived from pilocytic astrocytomas (grade 1). FGFR1 activity was stimulated by addition of FGF2. The activity of three FGFR1 inhibitors on cell migration after stimulation was assessed by live cell imaging and in a 3D spheroid invasion assay. FGFR1 levels in low and high-grade paediatric and adult tumour types were investigated in a commercial tissue microarray (TMA).RESULTSFGFR1 was found to be expressed among all cell lines examined by immunofluorescence. Phosphorylated (activated) FGFR1 was elevated in some cell lines after stimulation with FGF2. Live cell imaging of inhibitor-treated cells and spheroid invasion assays suggest pro-migratory effects of FGFR1 inhibition in low-grade versus anti-migratory in high-grade tumours. High FGFR1 expression in astrocytomas from patients aged under 18 compared to the 18–60 age group (χ2 = 11.578, p = 0.0031) was determined in the TMA sample set. There was a significant association of high FGFR1 levels with grade 2 and 3 astrocytomas.DISCUSSIONWe report the presence of FGFR1 among low and high-grade paediatric gliomas and a role in cell migration after stimulation with ligand. Treatment with FGFR1 inhibitors may elicit a different effect on cell migration depending on tumour grade.

U2 - 10.1093/neuonc/nox.238.108

DO - 10.1093/neuonc/nox.238.108

M3 - Meeting Abstract

SP - 24

JO - Neuro-Oncology

JF - Neuro-Oncology

SN - 1522-8517

ER -

Egbivwie N, Warr T, Humphries M, Esteves F, Short SC, Cockle JV et al. A role for FGFR1 in paediatric gliomas. Neuro-Oncology. 2018 Jan;24. https://doi.org/10.1093/neuonc/nox.238.108