Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution
Journal article, 2016

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.

inflammation

missing-self-recognition

il-6

natural-killer-cells

physical-activity

muscle

exercise

phenotype

cytokines

cancer

Author

L. Pedersen

University of Copenhagen

M. Idorn

Copenhagen University Hospital

G. H. Olofsson

Copenhagen University Hospital

B. Lauenborg

University of Copenhagen

Intawat Nookaew

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

R. H. Hansen

Amtssygehuset i Herlev

H. H. Johannesen

Amtssygehuset i Herlev

J. C. Becker

Universitats Klinikum Essen und Medizinische Fakultat

K. S. Pedersen

University of Copenhagen

C. Dethlefsen

University of Copenhagen

Jens B Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

J. Gehl

Copenhagen University Hospital

B. K. Pedersen

University of Copenhagen

P. T. Straten

University of Copenhagen

Copenhagen University Hospital

P. Hojman

University of Copenhagen

Copenhagen University Hospital

Cell Metabolism

1550-4131 (ISSN)

Vol. 23 3 554-562

Subject Categories

Cell Biology

Areas of Advance

Life Science Engineering (2010-2018)

DOI

10.1016/j.cmet.2016.01.011

PubMed

26895752

More information

Latest update

5/8/2018 1