神经系统在肿瘤发生和发展中的作用
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摘要
肿瘤在机体内不是一个孤立的结构,肿瘤组织内有神经纤维分布,肿瘤细胞表面存在着多种神经递质受体,神经递质触发受体后信号通路可调控肿瘤细胞的增殖、血管生成、侵袭和转移。神经系统还可通过调节免疫细胞的分化、增殖和活化,影响抗肿瘤免疫。肿瘤细胞释放的细胞因子可刺激感觉传入纤维或穿过血脑屏障,影响中枢神经系统的功能。心理社会应激会影响交感神经系统或下丘脑-垂体-肾上腺轴的功能,改变儿茶酚胺类神经递质和脑源性神经营养因子的水平而影响肿瘤的生长和发展。基于肿瘤发生和发展中神经系统的潜在作用,神经系统干预在肿瘤的全身干预疗法中是一个颇有前景的新领域。
Tumors are not isolated structures within organisms.Tumor tissue innervation has been confirmed,and neurotransmitters can directly regulate proliferation,angiogenesis,invasion and metastasis of tumors through acting on kinds of receptors on tumor cells,meanwhile,through acting on receptors on immune cells.Neurotransmitters can modulate differentiation,proliferation and activation of immune cells and influence tumor immune response.Correspondingly,cytokines released from tumor cells stimulate afferent sensory fibers or traverse blood-brain barrier,and affect the activities of central nervous system.Psychosociological stress can influence sympathetic system or hypothalamic-pituitaryadrenal axis,and cause variation of the levels of catecholamines and brain-derived neurotrophic factor(BDNF),which may affect initiation and progression of tumors.Based on the potential role of neuromodulation in initiation and progression of tumors,intervention targeting nervous system would be a promising strategy in systemic intervention of tumors.
Tumors are not isolated structures within organisms.Tumor tissue innervation has been confirmed,and neurotransmitters can directly regulate proliferation,angiogenesis,invasion and metastasis of tumors through acting on kinds of receptors on tumor cells,meanwhile,through acting on receptors on immune cells.Neurotransmitters can modulate differentiation,proliferation and activation of immune cells and influence tumor immune response.Correspondingly,cytokines released from tumor cells stimulate afferent sensory fibers or traverse blood-brain barrier,and affect the activities of central nervous system.Psychosociological stress can influence sympathetic system or hypothalamic-pituitaryadrenal axis,and cause variation of the levels of catecholamines and brain-derived neurotrophic factor(BDNF),which may affect initiation and progression of tumors.Based on the potential role of neuromodulation in initiation and progression of tumors,intervention targeting nervous system would be a promising strategy in systemic intervention of tumors.
引文
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[24]Chakroborty D,Chowdhury UR,Sarkar C,et al.Dopamine regulates endothelial progenitor cell mobilization from mouse bone marrow in tumor vascularization[J].J Clin Invest,2008,118(4):1380-1389.
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[27]Sloan EK,Priceman SJ,Cox BF,et al.The sympathetic nervous system induces a metastatic switch in primary breast cancer[J].Cancer Res,2010,70(18):7042-7052.
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[41]Kaiser MJ,Tiegs G,Neuhuber WL.Close apposition of dynorphinpositive nerve fibres to lymphocytes in the liver suggests opioidergic neuroi mmunomodulation[J].Histochem Cell Biol,2003,120(3):213-221.
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[48]Basu S,Dasgupta PS.Dopamine,a neurotransmitter,influences the immune system[J].J Neuroimmunol,2000,102(2):113-124.
[49]Pacheco R,Prado CE,Barrientos MJ,et al.Role of dopamine in the physiology of T-cells and dendritic cells[J].J Neuroimmunol,2009,216(1-2):8-19.
[50]Yang P,Li QJ,Feng Y,et al.TGF-betamiR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma[J].Cancer Cell,2012,22(3):291-303.
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