Xu Zhifang, Shioda Seiji, Masahisa Jinushi, Kawakami Yutaka, Ohtaki Hirokazu, Lim Huimin Calista, Wang Shenjun, Zhao Xue, Liu Yangyang, Zhou Dan, Guo Yi
Acu-moxibustion and Tuina Department, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582. Japan.
Curr Pharm Des. 2017;23(11):1687-1692. doi: 10.2174/1381612822666161025152942.
Although evidence over the last 30 years suggests that the autonomic nervous system (ANS) mediates stress-induced allostatic and immune responses, the crucial role that it plays in the tumor micro-environment has only recently been reported. Here, we review the action of ANS signaling in this micro-environment. Emerging data suggest that primary tumors are innervated by the ANS which mediates stress-related effects on tumor progression. The activation of the sympathetic nervous system (SNS) takes advantage of neurotransmitters and neuropeptides from the innervating neural circuitry and/or hypothalamic-pituitary-adrenal axis glucocorticoids via their receptors to modulate the gene expression associated with oncogenesis, the proliferation and apoptosis of tumor cells, angiogenesis, and the tumor-associated immune response. The parasympathetic nervous system has also been implicated in some tumor types, but its contribution in the tumor micro-environment remains unclear. In addition to identifying the ANS signaling pathways involved in tumor progression, recent reports suggest that the ANS could be a potential biomarker to predict tumor progression, and have identified new pharmacological strategies, such as the use of β-adrenergic blockers, to inhibit tumor progression and metastasis by targeting this system. These findings are reviewed here.
尽管过去30年的证据表明自主神经系统（ANS）介导应激诱导的适应性和免疫反应，但它在肿瘤微环境中所起的关键作用直到最近才被报道。在此，我们综述了ANS信号在这种微环境中的作用。新出现的数据表明，原发性肿瘤受ANS支配，ANS介导应激对肿瘤进展的相关影响。交感神经系统（SNS）的激活通过其受体利用来自支配神经回路和/或下丘脑-垂体-肾上腺轴糖皮质激素的神经递质和神经肽，来调节与肿瘤发生、肿瘤细胞增殖和凋亡、血管生成以及肿瘤相关免疫反应相关的基因表达。副交感神经系统也与某些肿瘤类型有关，但其在肿瘤微环境中的作用仍不清楚。除了确定参与肿瘤进展的ANS信号通路外，最近的报告表明，ANS可能是预测肿瘤进展的潜在生物标志物，并已确定了新的药理学策略，如使用β-肾上腺素能阻滞剂，通过靶向该系统来抑制肿瘤进展和转移。本文对这些发现进行了综述。
