Glioblastoma Cells Induce Neuron Loss In Vivo and In Vitro
Komal N Rawal1, Charlotte Degorre1, Philip J Tofilon1
1Radiation Oncology Branch, National Cancer Institute, 10 Center Drive-MSC 1002, Building 10, B3B406, Bethesda, MD 20892, USA.
Cancers
|September 13, 2025
Summary
Glioblastoma (GBM) cells kill neurons, especially after radiation therapy. This neurotoxicity involves Interleukin-8 (IL-8) and direct tumor cell-neuron interactions, impacting brain tumor recurrence.
Area of Science:
- Neuro-oncology
- Cancer biology
- Cellular neuroscience
Background:
- Glioblastoma (GBM) frequently recurs post-treatment, with seizures suggesting neuron toxicity.
- Tumor cell-neuron interactions are critical in GBM development, but their impact on neurons is not fully understood.
Purpose of the Study:
- To investigate the impact of Glioblastoma Stem Cells (GSCs) on neurons, particularly after radiotherapy.
- To elucidate the mechanisms underlying GSC-mediated neurotoxicity.
Main Methods:
- Orthotopic xenografts of GSCs in mice, followed by irradiation and immunohistochemistry.
- Direct co-culture of human GSCs and human induced pluripotent stem cell-derived neurons.
- Cytokine profiling of co-culture conditioned media (CM) and assessment of neuronal cell counts.
Main Results:
- Irradiated GBM xenografts showed reduced invasiveness and fewer associated neurons.
- Glioblastoma Stem Cells induced significant neuronal death in vitro, both directly and via conditioned media.
- Interleukin-8 (IL-8) was identified as a key mediator of GSC-induced neurotoxicity, with IL-8 blocking antibodies preventing neuronal death.
Conclusions:
- GBM regrowth after radiation is associated with neuronal loss.
- Direct GSC-neuron interaction is essential for GSC-mediated neurotoxicity.
- Interleukin-8 plays a critical role in Glioblastoma Stem Cell-induced neuronal death.
Keywords:
GSC–neuron cocultureGlioblastomaGlioblastoma stem cellsNeuron differentiationiPSC-derived Neuron Progenitor Cellsneuron deathMore Related Videos
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