Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution
Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution
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DOI：
10.1016/j.cmet.2016.01.011
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发表时间：
2016-03-08
期刊：
影响因子：
29
通讯作者：
Hojman, Pernille
中科院分区：
文献类型：
--
作者：
Pedersen, Line;Idorn, Manja;Hojman, Pernille
定期锻炼可以降低癌症和疾病复发的风险。然而这种保护背后的机制仍有待阐明。在这项研究中，荷瘤小鼠随机接受自愿轮跑，五种不同肿瘤模型的肿瘤发病率和生长速度降低了 60% 以上。微阵列分析揭示了训练诱导的与免疫功能相关途径的上调。跑步小鼠的肿瘤中 NK 细胞浸润显着增加，而 NK 细胞的耗竭会促进肿瘤生长并削弱运动的有益效果。机制分析表明，NK 细胞是由肾上腺素动员的，而β-肾上腺素信号传导的阻断会削弱训练依赖性的肿瘤抑制作用。此外，肾上腺素诱导 IL-6 敏感 NK 细胞的选择性动员，IL-6 阻断抗体削弱了训练诱导的肿瘤抑制、瘤内 NK 细胞浸润和 NK 细胞激活。总之，这些结果将运动、肾上腺素和 IL-6 与 NK 细胞动员和重新分布联系起来，并最终控制肿瘤生长。
Regular exercise reduces the risk of cancer and disease recurrence. Yet the mechanisms behind this protection remain to be elucidated. In this study, tumor-bearing mice randomized to voluntary wheel running showed over 60% reduction in tumor incidence and growth across five different tumor models. Microarray analysis revealed training-induced up-regulation of pathways associated with immune function. NK cell infiltration was significantly increased in tumors from running mice, whereas depletion of NK cells enhanced tumor growth and blunted the beneficial effects of exercise. Mechanistic analyses showed that NK cells were mobilized by epinephrine, and blockade of beta-adrenergic signaling blunted training-dependent tumor inhibition. Moreover, epinephrine induced a selective mobilization of IL-6-sensitive NK cells, and IL-6-blocking antibodies blunted training-induced tumor suppression, intratumoral NK cell infiltration, and NK cell activation. Together, these results link exercise, epinephrine, and IL-6 to NK cell mobilization and redistribution, and ultimately to control of tumor growth.