跑步减缓肿瘤生长的机制-运动产生的细胞因子把癌细胞杀手NK细胞引导进入肿瘤组织
Running helps mice slow cancer growth
跑步的健康益处包括增强呼吸和心血管系统的健康、减肥、保持年轻的外表、预防肌肉和骨质流失、刺激生长激素的释放、预防中风、糖尿病和高血压…现在，丹麦歌本哈哥大学的科学家不仅证实了跑步可以缓慢肿瘤的生长，而且还找到跑步减缓肿瘤生长的机制。
在本研究中，科学家发现，把空闲时间花在跑步机上的老鼠比那些不那么活跃的老鼠能更好地收缩肿瘤(肿瘤体积缩小了50%)。研究人员发现，伴随着高强度锻炼而来的肾上腺素（Epinephrine）激增，有助于将杀死癌症的免疫细胞(NK细胞)转移到小鼠的肺、肝脏或皮肤肿瘤上。该研究发表在2016年2月16日在专业杂志 “CELL METABOLISM细胞代谢”。
“众所周知，自然杀伤细胞(NK)的渗透可以控制和调节肿瘤的大小，但没有人研究过运动是如何调节系统的，”哥本哈根大学的资深研究作者佩尼耶·霍曼说。“在我们的实验中,我们把肾上腺素注入小鼠，模仿增加你在运动过程中看到的情况。在实验中，我们看到，NK细胞动员到血液中，然后如果有肿瘤存在，NK细胞会发现肿瘤和聚集在肿瘤的周围。”
Hojman和她的同事接下来使用了耗尽NK细胞的小鼠，以证明肿瘤部位NK细胞数量的增加直接导致了肿瘤体积的的缩小。即使有了运动和其他免疫细胞，没有NK细胞，这些小鼠也经历了正常的癌症生长速度。
图示：众所周知，NK细胞癌细胞杀手。运动是肌肉释放的细胞因子IL-6引导NK细胞进入肿瘤。
阻断肾上腺素的功能也降低了跑步机的抗癌效果。该研究小组还发现，一种名为IL-6的免疫信号分子，是NK细胞的肾上腺素依赖性动员与肿瘤浸润之间的联系。众所周知，IL-6在运动过程中会从肌肉组织中释放出来，但是Hojman提供的证据表明，肾上腺素尤其会影响IL-6敏感的NK细胞，而IL-6分子有助于引导免疫细胞进入肿瘤。
“这对我们来说是一个很大的惊喜，”她说，并补充说，IL-6及其在肿瘤生物学中的作用可能是一个有争议的话题。“在这项研究中，我们证明了运动诱导的IL-6似乎在NK细胞的归巢和激活NK细胞中起了一定的作用。”虽然这项研究对寻找治疗癌症的廉价方法充满希望，但更多的需要了解运动对转移和寿命的影响，以及对人类的观察是否正确。Hojman还想探讨抗癌治疗和运动对肿瘤的综合影响。作为一个在运动和肿瘤学领域工作的人，癌症患者经常问的一个主要问题是:我该如何锻炼?我们能做点什么吗?”她说。“虽然以前很难向人们提供锻炼强度的建议，但我们的数据表明，为了激发良好的肾上腺素激增，并因此招募NK细胞，锻炼强度可能会有所提高。”
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Running helps mice slow cancer growth
Date:
February 16, 2016
Summary:
Here's one more benefit of exercise: mice who spent their free time on a running wheel were better able to shrink tumors (a 50 percent reduction in tumor size) compared to their less active counterparts. Researchers found that the surge of adrenaline that comes with a high-intensity workout helped to move cancer-killing immune (NK) cells toward lung, liver, or skin tumors implanted into the mice.
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Here's one more benefit of exercise: mice who spent their free time on a running wheel were better able to shrink tumors (a 50% reduction in tumor size) compared to their less active counterparts. (Stock image)
Credit: © Szasz-Fabian Jozsef / Fotolia
Here's one more benefit of exercise: mice who spent their free time on a running wheel were better able to shrink tumors (a 50% reduction in tumor size) compared to their less active counterparts. Researchers found that the surge of adrenaline that comes with a high-intensity workout helped to move cancer-killing immune (NK) cells toward lung, liver, or skin tumors implanted into the mice. The study appears Feb. 16, 2016 in Cell Metabolism.
"It is known that infiltration of natural killer (NK) immune cells can control and regulate the size of tumors, but nobody had looked at how exercise regulates the system," says senior study author Pernille Hojman, at the University of Copenhagen. "In our experiments, we tried to inject our mice with adrenaline to mimic this increase you see during exercise, and when we do that we see that the NK cells are mobilized to the bloodstream, and if there's a tumor present then the NK cells will find the tumor and home to it."
Hojman and her colleagues next used mice depleted of NK cells to show that the increase in number of NK cells at the site of the tumor was directly contributing to the reduction in size. Even with exercise and a full suite of other immune cells, without the NK cells these mice experienced the normal rate of cancer growth. Blocking the function of adrenaline also blunted the cancer-killing benefits of the running wheel.
The research group also discovered that an immune signaling molecule called IL-6 was the link between adrenaline-dependent mobilization of NK cells and tumor infiltration. It's known that IL-6 is released from muscle tissue during exercise, but Hojman presents evidence that adrenaline specifically hails IL-6 sensitive NK cells and that the IL-6 molecules helped guide the immune cells to the tumors.
"That was actually a big surprise to us," she says, adding that IL-6 and its role in tumor biology can be a controversial topic. "In this study we show that the exercise-induced IL-6 seems to play a role in homing of NK cells to the tumor and also in the activation of those NK cells."
While the research is hopeful for patients looking for inexpensive ways to manage their cancer, more needs to be learned about the effects of exercise on metastasis and longevity, as well as if the observations hold true in humans. Hojman also wants to explore the combined impact of anti-cancer treatments and exercise on tumors.
"As someone working in the field of exercise and oncology, one of the main questions that cancer patients always ask is: how should I exercise? Can we do anything?" she says. "While it has previously been difficult to advise people about the intensity at which they should exercise, our data suggest that it might be beneficial to exercise at a somewhat high intensity in order to provoke a good epinephrine surge and hence recruitment of NK cells."
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Materials provided by Cell Press. Note: Content may be edited for style and length.
Journal Reference:
Line Pedersen et al. Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution. Cell Metabolism, February 2016 DOI: 10.1016/j.cmet.2016.01.011
-- ScienceDaily https://www.sciencedaily.com/releases/2016/02/160216142825.htm
