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Updated: Mar 12, 2026
Translational Orthotopic Models of Glioblastoma Multiforme
Published on: February 17, 2023
No role of IFITM3 in brain tumor formation in vivo
Nevenka Dudvarski Stankovic1,2,3, Nicola Hoppmann4, Marcin Teodorczyk1
1Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, School of Medicine, Mainz, Germany.
Abstract:
Glioblastoma multiforme (GBM) is one of the most lethal solid tumors in adults. Despite aggressive treatment approaches for patients, GBM recurrence is inevitable, in part due to the existence of stem-like brain tumor-propagating cells (BTPCs), which produce factors rendering them resistant to radio- and chemotherapy. Comparative transcriptome analysis of irradiated, patient-derived BTPCs revealed a significant upregulation of the interferon-inducible transmembrane protein 3 (IFITM3), suggesting the protein as a factor mediating radio resistance. Previously, IFITM3 has been described to affect glioma cells; therefore, the role of IFITM3 in the formation and progression of brain tumors has been investigated in vivo. Intracranial implantation studies using radio-selected BTPCs alongside non-irradiated parental BTPCs in immunodeficient mice displayed no influence of irradiation on animal survival. Furthermore, gain and loss of function studies using BTPCs ectopically expressing IFITM3 or having IFITM3 down-modulated by a shRNA approach, did affect neither tumor growth nor animal survival. Additionally, a syngeneic model based on the mouse glioma cell line GL261 was applied in order to consider the possibility that IFITM3 relies on an intact immune system to unfold its tumorigenic potential. GL261 cells ectopically expressing IFITM3 were implanted into the striatum of immunocompetent mice without influencing the survival of glioma-bearing animals. Lastly, the vasculature and the extent of microglia/macrophage invasion into the tumor were studied in BTPC and GL261 tumors but neither parameter was altered by IFITM3. This report presents for the first time that IFITM3 is upregulated in patient-derived BTPCs upon irradiation but does not affect brain tumor formation or progression in vivo.
Insights
Interferon-inducible transmembrane protein 3 (IFITM3) is upregulated in brain tumor-propagating cells (BTPCs) after irradiation. However, IFITM3 does not influence brain tumor formation or progression in vivo.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Glioblastoma multiforme (GBM) is a highly lethal adult brain tumor.
- GBM recurrence is often due to radio- and chemo-resistant brain tumor-propagating cells (BTPCs).
- Interferon-inducible transmembrane protein 3 (IFITM3) is upregulated in BTPCs post-irradiation, suggesting a role in radioresistance.
Purpose of the Study:
- To investigate the in vivo role of IFITM3 in brain tumor formation and progression.
- To determine if IFITM3 influences radioresistance in BTPCs.
- To assess IFITM3's impact on tumor growth and survival in both immunocompromised and immunocompetent models.
Main Methods:
- Comparative transcriptome analysis of irradiated and non-irradiated patient-derived BTPCs.
- In vivo intracranial implantation of radio-selected and parental BTPCs in immunodeficient mice.
- Gain and loss of function studies of IFITM3 in BTPCs using ectopic expression and shRNA.
- Implantation of IFITM3-expressing GL261 glioma cells into immunocompetent mice.
- Analysis of tumor vasculature and microglia/macrophage infiltration.
Main Results:
- Irradiation of BTPCs led to significant IFITM3 upregulation.
- IFITM3 expression levels did not affect animal survival in BTPC implantation studies.
- Modulating IFITM3 expression (gain/loss of function) did not alter tumor growth or survival.
- IFITM3 expression in GL261 cells did not impact survival in immunocompetent mice.
- IFITM3 did not alter tumor vasculature or immune cell infiltration.
Conclusions:
- IFITM3 is upregulated in BTPCs following irradiation.
- Despite upregulation, IFITM3 does not appear to mediate radioresistance or affect brain tumor progression in vivo.
- The tumorigenic potential of IFITM3 is not dependent on an intact immune system in the studied models.
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