Neural activity promotes tumor growth, and tumor-secreted factors promote neural activity. Krishna et al. used electrocorticography to record from tumor-infiltrated and normal-appearing cortex in awake adults with glioblastoma while they performed cognitive tasks during surgery. The authors found that high-gamma band power was higher in tumor-infiltrated than in non-tumor areas of cortex, which may reflect hyperexcitability in tumor-infiltrated cortex. They used magnetoencephalography to measure functional connectivity (FC) of regions within the tumor, and transcriptomics and histology to compare gene expression in resected tissues with high or low FC. The ‘high-FC’ tissues had increased expression of axon guidance and synapse-related genes, including that encoding the astrocyte-secreted synaptogenic molecule THBS1, and a higher density of synaptic puncta. Co-culturing neural organoids with high-FC resected tissue promoted synapse formation and increased neural synchrony. Xenografting high-FC tissue into mouse hippocampus led to larger numbers of synapses, increased tumor proliferation, and decreased mouse survival compared to xenografting low-FC tissues. A higher degree of tumor FC in patients with glioblastoma was similarly associated with reduced survival. By integrating clinical, cognitive, and cellular neuroscience, this study provides insight into the relationship between neural activity and tumor progression, and nominates pathways for therapeutic intervention.
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