Glioblastoma Cell Growth is Suppressed by Disruption of Fibroblast Growth Factor Pathway Signaling

Overview

Journal J Neurooncol

Publisher Springer

Date 2009 Apr 3

PMID 19340397

Citations 48

Authors

Watcharin Loilome

Avadhut D Joshi

Colette M J ap Rhys

Sara Piccirillo

Angelo L Vescovi

Vescovi L Angelo

Gary L Gallia

Gregory J Riggins

Affiliations

Soon will be listed here.

Abstract

The Fibroblast Growth Factor (FGF) signaling pathway is reported to stimulate glioblastoma (GBM) growth. In this work we evaluated the effect of FGF2, FGF receptor (FGFR), and small molecule inhibition on GBM cells grown in traditional media, or cultured directly in stem-cell media. These lines each expressed the FGFR1, FGFR3 and FGFR4 receptors. Addition of FGF2 ligand showed significant growth stimulation in 8 of 10 cell lines. Disruption of FGF signaling by a neutralizing FGF2 monoclonal antibody and FGFR1 suppression by RNA interference both partially inhibited cell proliferation. Growth inhibition was temporally correlated with a reduction in MAPK signaling. A receptor tyrosine kinase inhibitor with known FGFR/VEGFR activity, PD173074, showed reproducible growth inhibition. Possible mechanisms of growth suppression by PD173074 were implicated by reduced phosphorylation of AKT and MAPK, known oncogenic signal transducers. Subsequent reduction in the cyclin D1, cyclin D2 and CDK4 cell cycle regulators was also observed. Our results indicate that FGF signaling pathway inhibition as a monotherapy will slow, but not arrest growth of glioblastoma cells.

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