Neuronal Reshaping of the Tumor Microenvironment in Tumorigenesis and Metastasis: Bench to Clinic

作者：Yangmin Wu, Ruowei Sun, Shuai Ren, Gökhan Zengin, Mengyao Li · 发表于：Medicine Advances · 年份：2025 · DOI：10.1002/med4.70044 · 被引用次数：23 · 研究领域：Cancer, Stress, Anesthesia, and Immune Response、Glioma Diagnosis and Treatment、Neuroblastoma Research and Treatments

This graphical abstract illustrates the multidimensional crosstalk between neurons and tumor microenvironment as well as targeted intervention strategies identified in the study. It highlights three core interaction axes: nerve-tumor crosstalk mediated by neurotransmitters and neurotrophic factors, neuro-vascular communication driving angiogenesis via Norepinephrine/β2-Adrenergic Receptor/Vascular Endothelial Growth Factor signaling, and neuro-immune regulation involving Myeloid-Derived Suppressor Cells and M2 macrophage polarization. The central panel reveals the key mechanism: psychological stress activates sympathetic nerves, which downregulates tumor cell AlkB Homolog 5 via NE/Adrenoceptor Beta 2, leading to m6A-RNA packaging into extracellular vesicles that promote neural overactivation. The right and bottom panels present effective interventions, including radiotherapy + perampanel, fisetin (inhibiting extracellular vesicles uptake), Glial Cell Line-Derived Neurotrophic Factor-neutralizing antibody, and sympathetic denervation, which collectively suppress tumor progression and metastasis.