Voluntary running suppresses tumor growth through epinephrine- and IL-6-dependent NK cell mobilization and redistribution

Journal Article · Tue Feb 16 04:00:00 EST 2016 · Cell Metabolism

DOI:https://doi.org/10.1016/j.cmet.2016.01.011· OSTI ID:1335309

Pedersen, Line ^[1]; Idorn, Manja ^[2]; Olofsson, Gitte H. ^[2]; Lauenborg, Britt ^[1]; Nookaew, Intawat ^[3]; Hansen, Rasmus Hvass ^[4]; Johannesen, Helle Hjorth ^[4]; Becker, Jurgen C. ^[5]; Pedersen, Katrine S. ^[1]; Dethlefsen, Christine ^[1]; Nielsen, Jens ^[6]; Gehl, Julie ^[2]; Pedersen, Bente K. ^[1]; thor Straten, Per ^[7]; Hojman, Pernille ^[8]

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1. Univ. of Copenhagen (Denmark)
2. Copenhagen Univ. Hospital, Herlev (Denmark)
3. Chalmers Univ. of Technology, Goteborg (Sweden); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
4. Univ. Hospital Copenhagen, Herlev (Denmark)
5. Univ. Hospital Essen, Essen (Germany)
6. Chalmers Univ. of Technology, Goteborg (Sweden)
7. Copenhagen Univ. Hospital, Herlev (Denmark); Univ. of Copenhagen (Denmark)
8. Univ. of Copenhagen (Denmark); Copenhagen Univ. Hospital, Herlev (Denmark)

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. Altogether, these results link exercise, epinephrine, and IL-6 to NK cell mobilization and redistribution, and ultimately to control of tumor growth.

• Research Organization: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-00OR22725
• OSTI ID: 1335309
• Journal Information: Cell Metabolism, Journal Name: Cell Metabolism Journal Issue: 3 Vol. 23; ISSN 1550-4131
• Publisher: Cell Press
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
adrenalin
cancer
epinephrine
exercise
exercise oncology
immune cells
interleukin 6
natural killer cells
physical activity