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Basic fibroblast growth factor binding and processing by human glioma cells

P R Murphy1, R S Knee

  • 1Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.

Molecular and Cellular Endocrinology
|October 30, 1995
PubMed
Summary
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Tumor cells utilize basic fibroblast growth factor (bFGF) for growth. This study reveals that glioma cells express bFGF receptors (FGFRs), which are regulated by bFGF, and heparan sulfate proteoglycans may aid bFGF presentation to FGFRs.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Glial tumor cells, such as gliomas, often overexpress basic fibroblast growth factor (bFGF).
  • bFGF acts in an autocrine manner, stimulating tumor cell proliferation.
  • Understanding bFGF receptor (FGFR) dynamics in these cells is crucial for targeted therapies.

Purpose of the Study:

  • To investigate the expression, binding, and processing of bFGF receptors (FGFRs) in a human glioma cell line (U87-MG).
  • To elucidate the role of endogenous bFGF and heparan sulfate proteoglycans in FGFR regulation and function.

Main Methods:

  • Reverse transcription-polymerase chain reaction (RT-PCR) to detect FGFR mRNA.
  • 125I-bFGF crosslinking and Western blotting to identify and characterize FGFRs.

Related Experiment Videos

  • Suramin treatment to assess receptor regulation.
  • Heparin and heparinase digestion to investigate the role of heparan sulfate proteoglycans.
  • Scatchard binding analysis to quantify high-affinity binding sites.

    • Main Results:

    • U87-MG cells express both bFGF and FGFR mRNAs.
    • A 110-kDa high-affinity FGFR, consistent with FGFR-1, was identified on the cell membrane.
    • Endogenous bFGF down-regulates FGFR expression and binding sites, as shown by suramin treatment.
    • Removal of extracellular bFGF rapidly increases high-affinity binding sites.
    • Heparan sulfate proteoglycans appear to facilitate bFGF presentation to FGFRs but are not essential for high-affinity binding.

    Conclusions:

    • Human glioma cells express functional FGFRs that are subject to autocrine regulation by bFGF.
    • Heparan sulfate proteoglycans play a modulatory role in bFGF-FGFR interactions.
    • These findings provide insights into bFGF signaling pathways in gliomas, potentially informing therapeutic strategies.