Neuronal Activity and Tumor Growth in Glioma Systems

Recent advances have revealed that glioma cells form functional interfaces with neurons, exploiting both synaptic and paracrine signalling to drive tumour progression. Electrically active circuits release neuroligin-3 and brain-derived neurotrophic factor (BDNF), which promote glioma cell proliferation via AMPA receptor-mediated depolarisation and downstream kinase signalling. Concurrently, gliomas remodel host networks by secreting synaptogenic factors and extending tumour microtubes that interconnect cancer cells and support metabolic transfer. An epigenetically defined “neural” tumour state characterised by hypomethylation of synapse-related genes correlates with enhanced neuronal integration and poorer patient outcome. Together, these findings establish bidirectional neuron–glioma interactions as key determinants of invasive growth, cognitive dysfunction and therapeutic resistance, informing emerging strategies to disrupt malignant circuitry and improve prognosis.

Research from Nature Portfolio

A study in adult patients undergoing language mapping demonstrated that high-grade gliomas remodel functional neural circuits beyond normal task-related regions. Tumour-infiltrated cortex enriched for a synaptogenic subpopulation secretes thrombospondin-1, which augments neuron–glioma connectivity, impairs cognition and shortens survival. Pharmacological blockade of thrombospondin-1 with gabapentin reduced glioma proliferation, highlighting a repurposing opportunity. An epigenetic investigation classified glioblastomas into low- or high-neural subtypes by DNA methylation profiles. High-neural tumours upregulate synaptic integration genes, form neuron-to-glioma synapses in model systems, exhibit increased functional connectivity on magnetoencephalography and carry a worse prognosis. Plasma biomarkers reflecting this neural signature further suggest non-invasive patient stratification. In mechanistic work, BDNF–TrkB signalling was shown to regulate malignant synaptic plasticity. Activity-dependent BDNF secretion promotes AMPA receptor trafficking to glioma membranes via CAMKII, amplifying glutamate-evoked currents and proliferation. Genetic or pharmacological TrkB inhibition reduced synapse number, abrogated tumour potentiation and extended survival in xenografts, demonstrating a novel target to interrupt tumour-driven plasticity.

Neuronal Activity and Tumor Growth in Glioma Systems publication trend

The graph below shows the total number of articles in neuronal activity and tumor growth in glioma systems across all publications each year (not limited to Nature Index journals).

Technical terms

Neuron-to-glioma synapse: A functional junction where a neuron releases neurotransmitter to depolarise a glioma cell, promoting tumour proliferation.

Neuroligin-3: A synaptic adhesion protein secreted by active neurons that stimulates glioma growth via paracrine signalling.

BDNF–TrkB signalling: Neurotrophin binding to tropomyosin receptor kinase B on glioma cells, driving synaptic plasticity and proliferation.

Tumour microtube: Long, neurite-like protrusion extended by glioma cells to interconnect and share resources across the tumour network.

Functional connectivity: The statistical coherence of activity between brain regions or tumour and brain measured by techniques such as magnetoencephalography or resting-state MRI.

References

1. Glioblastoma remodelling of human neural circuits decreases survival. Nature (2023).
2. A prognostic neural epigenetic signature in high-grade glioma. Nature Medicine (2024).
3. Characterizing and targeting glioblastoma neuron-tumor networks with retrograde tracing. Cell (2024).
4. Tumor microenvironment in glioblastoma: Current and emerging concepts. Neuro-Oncology Advances (2023).
5. Oscillatory brain activity associates with neuroligin-3 expression and predicts progression free survival in patients with diffuse glioma. Journal of Neuro-Oncology (2018).