Journal of Neuro-Oncology

, Volume 94, Issue 3, pp 359–366

Glioblastoma cell growth is suppressed by disruption of fibroblast growth factor pathway signaling

  • Watcharin Loilome
  • Avadhut D. Joshi
  • Colette M. J. ap Rhys
  • Sara Piccirillo
  • Vescovi L. Angelo
  • Gary L. Gallia
  • Gregory J. Riggins
Laboratory Investigation - human/animal tissue

DOI: 10.1007/s11060-009-9885-5

Cite this article as:
Loilome, W., Joshi, A.D., ap Rhys, C.M.J. et al. J Neurooncol (2009) 94: 359. doi:10.1007/s11060-009-9885-5

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.

Keywords

Glioblastoma GBM stem-like cell Fibroblast growth factor signaling pathway 

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Watcharin Loilome
    • 1
    • 2
  • Avadhut D. Joshi
    • 1
  • Colette M. J. ap Rhys
    • 1
  • Sara Piccirillo
    • 3
  • Vescovi L. Angelo
    • 3
  • Gary L. Gallia
    • 1
  • Gregory J. Riggins
    • 1
  1. 1.Department of Neurosurgery, School of MedicineJohns Hopkins UniversityBaltimoreUSA
  2. 2.Department of Biochemistry, Faculty of MedicineKhon Kaen UniversityKhon KaenThailand
  3. 3.Università degli Studi Bicocca-MillanMilanItaly

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