Journal of Neuro-Oncology

, Volume 18, Issue 3, pp 207–216

Basic fibroblast growth factor and fibroblast growth factor receptor I are implicated in the growth of human astrocytomas

Authors

  • Richard S. Morrison
    • Department of NeurosurgeryThe University of Texas M.D. Anderson Cancer Center
    • Department of Tumor BiologyThe University of Texas M.D. Anderson Cancer Center
  • Fumio Yamaguchi
    • Department of NeurosurgeryThe University of Texas M.D. Anderson Cancer Center
  • Hideyuki Saya
    • Department of Tumor BiologyThe University of Texas M.D. Anderson Cancer Center
    • Department of Neuro OncologyThe University of Texas M.D. Anderson Cancer Center
  • Janet M. Bruner
    • Department of NeuropathologyThe University of Texas M.D. Anderson Cancer Center
  • Alan M. Yahanda
    • Department of Surgical OncologyThe University of Texas M.D. Anderson Cancer Center
  • Lawrence A. Donehower
    • Division of Molecular VirologyBaylor College of Medicine
  • Mitchel Berger
    • Department of NeurosurgeryUniversity of Washington
Article

DOI: 10.1007/BF01328955

Cite this article as:
Morrison, R.S., Yamaguchi, F., Saya, H. et al. J Neuro-Oncol (1994) 18: 207. doi:10.1007/BF01328955

Summary

Malignant astrocytomas are highly invasive, vascular neoplasms that comprise the majority of nervous system tumors in humans. A strong association has previously been made between malignancy in human astrocytic tumors and increased expression of certain fibroblast growth factor (FGF) family members, including basic and acidic FGF. The influence of endogenous basic FGF on glioblastoma cell growthin vitro was evaluated using basic FGF-specific antisense oligonucleotides. These studies indicated that human glioblastoma cell growthin vitro, can be inhibited by suppressing basic FGF expression. Human astrocytomas also exhibited changes in FGF receptor (FGFR) expression during the course of their progression from a benign to a malignant phenotype. FGFR2 (bek) expression was abundant in normal white matter and in all low grade astrocytomas, but was not observed in glioblastomas. Conversely, FGFR1 (flg) expression was absent or barely detectable in normal white matter, but was significantly elevated in glioblastomas. Glioblastomas also expressed an alternatively spliced form of FGFR1 containing two immunoglobulin-like disulfide loops (FGFR1β), whereas normal human adult and fetal brain expressed a form of the receptor containing three immunoglobulin-like disulfide loops (FGFR1α). Intermediate grades of astrocytic tumors exhibited a gradual loss of FGFR2 and a shift in expression from FGFR1α to FGFR1β as they progressed from a benigh to a malignant phenotype. The underlying cytogenetic changes that contribute to these alterations are not entirely understood, but abnormalities in the p53 tumor suppressor gene may influence expression of bFGF as well as the FGFR. These results suggest that alterations in FGFR signal transduction pathways may play a critical role in the malignant progression of astrocytic tumors.

Key words

brain tumorastrocytomagliomacentral nervous systemangiogenesismalignant progression

Copyright information

© Kluwer Academic Publishers 1994