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Updated: Aug 21, 2026
Fluorescence Molecular Tomography for In Vivo Imaging of Glioblastoma Xenografts
Published on: April 26, 2018
Inhibition of FGF receptor activity in glioma implanted into the mouse brain using the tetracyclin-regulated
Sylvain Miraux1, Sylvie Lemière, Raphael Pineau
1Magnetic Resonance Center, CNRS-University Victor Segalen Bordeaux 2, Bordeaux, France.
Abstract:
We have investigated growth and vascularization of malignant glioma in mice upon conditional inhibition of fibroblast growth factor (FGF) receptor activity. C6 rat glioma cells were transfected with a dominant-negative fibroblast growth factor receptor-2 (FGFR2-DN) cDNA under the control of a tetracycline-regulated expression promoter (tet off) and implanted in the brain of immunodeficient mice. Magnetic resonance imaging analysis showed a significant decrease in tumor growth 14 days after implantation when FGFR2-DN was expressed compared to control. This size difference disappeared after 20 days. However, after 20 days, tumor and endothelial cells apoptosis were higher in the FGFR2-DN group and consequently angiogenesis was decreased whereas tumor cells were similarly associated with blood vessels at the tumor periphery. Pericyte coverage was not different between the two groups but a higher amount of pericytes not associated with vessels was found in the FGFR2-DN expressing group. This demonstrates, that conditional expression of inhibitor of FGF receptor activity in gliomas implanted in the brain of immunodeficient mice can be achieved efficiently, and that FGFs are major players in glioma development and in glioma angiogenesis.
Insights
Inhibiting fibroblast growth factor (FGF) receptor activity in mouse gliomas reduced early tumor growth and angiogenesis. Later, increased apoptosis and decreased blood vessel formation were observed, highlighting FGFs' role in glioma development.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Research
Background:
- Malignant gliomas are aggressive brain tumors with poor prognosis.
- Fibroblast growth factors (FGFs) are implicated in tumor growth and angiogenesis.
- Targeting FGF receptor signaling is a potential therapeutic strategy for gliomas.
Purpose of the Study:
- To investigate the role of fibroblast growth factor (FGF) receptor activity in malignant glioma growth and vascularization.
- To assess the efficacy of conditional inhibition of FGF receptor-2 (FGFR2) in a preclinical glioma model.
Main Methods:
- C6 rat glioma cells expressing a dominant-negative FGFR2 (FGFR2-DN) under a tetracycline-regulated promoter were implanted in immunodeficient mice.
- Tumor growth was monitored using magnetic resonance imaging (MRI).
- Apoptosis, angiogenesis, and pericyte association with vessels were analyzed post-mortem.
Main Results:
- Conditional FGFR2-DN expression significantly reduced glioma size at 14 days post-implantation.
- Tumor size difference diminished by day 20, but apoptosis increased and angiogenesis decreased in the FGFR2-DN group.
- While tumor cells maintained association with blood vessels, increased non-vascular pericytes were noted in the FGFR2-DN group.
Conclusions:
- Conditional inhibition of FGF receptor activity is achievable in brain gliomas.
- FGF signaling is a critical driver of glioma development and angiogenesis.
- Targeting FGF receptors may offer therapeutic benefits for malignant gliomas.
