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) 19327420 (eISSN)
Vol. 23 3 554-562Subject Categories
Cell Biology
Areas of Advance
Life Science Engineering (2010-2018)
DOI
10.1016/j.cmet.2016.01.011
PubMed
26895752