Glioma‑neuronal interactions in tumor progression: Mechanism, therapeutic strategies and perspectives (Review)

Abstract

An increasing body of evidence has become available to reveal the synaptic and functional integration of glioma into the brain network, facilitating tumor progression. The novel discovery of glioma-neuronal interactions has fundamentally challenged our understanding of this refractory disease. The present review aimed to provide an overview of how the neuronal activities function through synapses, neurotransmitters, ion channels, gap junctions, tumor microtubes and neuronal molecules to establish communications with glioma, as well as a simplified explanation of the reciprocal effects of crosstalk on neuronal pathophysiology. In addition, the current state of therapeutic avenues targeting critical factors involved in glioma-euronal interactions is discussed and an overview of clinical trial data for further investigation is provided. Finally, newly emerging technologies, including immunomodulation, a neural stem cell-based delivery system, optogenetics techniques and co-culture of neuron organoids and glioma, are proposed, which may pave a way towards gaining deeper insight into both the mechanisms associated with neuron-and glioma-communicating networks and the development of therapeutic strategies to target this currently lethal brain tumor.

Neuronal acid-sensing ion channel 1a regulates neuron-to-glioma synapses

“…7 ). Neuronal hyperactivity promotes glioma proliferation by activating ion channels through glutamate secretion (Hua et al, 2022). These hyperexcitable neurons induce evoked ESCs in glioma cells mediated by AMPAR (Venkataramani et al, 2019; Venkatesh et al, 2019).…”

Chronic stress as an emerging risk factor for the development and progression of glioma

“…During this process, neurons also released neuroligin-3 to activate the PI3K-mammalian target of rapamycin pathway in glioma cells and promote the proliferation of glioma cells. [ 91 ] Although there are no relevant studies demonstrating that CS promotes excitatory synapse formation, Tantillo et al [ 92 ] found that gamma aminobutyric acidergic (GABAergic) interneuron activity was reduced in mice after chronic visual deprivation, a specific form of CS, resulting in increased glioma proliferation in the primary visual cortex. Unlike excitatory information transmitted by glutamatergic synapses, GABAergic neurons are the main inhibitory neurons in the CNS.…”

Therapeutic Targeting of Glioblastoma and the Interactions with Its Microenvironment

“…Similarly, GBM cells can influence neurons through the secretion of non-synaptic glutamate [62,63] and can reduce the activation of inhibitory interneurons [64]. Gliomas may also increase the risk of epilepsy by influencing glutamatergic and GABAergic signalling in neurons [65], with studies in awake patients observing more neuronal excitability in the GBM-infiltrated cortex [59]. Short-range electrocorticography on the tumour-infiltrated cortex revealed functional remodelling of language circuits as some tumour regions with TSP-1 + tumour cells maintained functional connectivity with neurons.…”