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

Line Pedersen; Manja Idorn; Gitte H. Olofsson; Britt Lauenborg; Intawat Nookaew; Rasmus Hvass Hansen; Helle Hjorth Johannesen; Jürgen C Becker; Katrine S. Pedersen; Christine Dethlefsen; Jens Nielsen; Julie Gehl; Bente Klarlund Pedersen; Per Thor Straten; Pernille Højman

doi:10.1016/j.cmet.2016.01.011

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

Line Pedersen, Manja Idorn, Gitte H. Olofsson, Britt Lauenborg, Intawat Nookaew, Rasmus Hvass Hansen, Helle Hjorth Johannesen, Jürgen C Becker, Katrine S. Pedersen, Christine Dethlefsen, Jens Nielsen, Julie Gehl, Bente Klarlund Pedersen, Per Thor Straten, Pernille Højman

Department of Clinical Medicine

290 Citations (Scopus)

Abstract

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 upregulation 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 β-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.

Original language	English
Journal	Cell Metabolism
Volume	23
Issue number	3
Pages (from-to)	554-562
ISSN	1550-4131
DOIs	https://doi.org/10.1016/j.cmet.2016.01.011
Publication status	Published - 8 Mar 2016

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Pedersen, L., Idorn, M., Olofsson, G. H., Lauenborg, B., Nookaew, I., Hansen, R. H., Johannesen, H. H., Becker, J. C., Pedersen, K. S., Dethlefsen, C., Nielsen, J., Gehl, J., Pedersen, B. K., Straten, P. T., & Højman, P. (2016). Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution. Cell Metabolism, 23(3), 554-562. https://doi.org/10.1016/j.cmet.2016.01.011

Pedersen, L, Idorn, M, Olofsson, GH, Lauenborg, B, Nookaew, I, Hansen, RH, Johannesen, HH, Becker, JC, Pedersen, KS, Dethlefsen, C, Nielsen, J, Gehl, J, Pedersen, BK , Straten, PT & Højman, P 2016, 'Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution', Cell Metabolism, vol. 23, no. 3, pp. 554-562. https://doi.org/10.1016/j.cmet.2016.01.011

@article{a3f9a9bf8a3648cb8e25ed6f950b6fb7,

title = "Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution",

abstract = "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 upregulation 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 β-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.",

author = "Line Pedersen and Manja Idorn and Olofsson, {Gitte H.} and Britt Lauenborg and Intawat Nookaew and Hansen, {Rasmus Hvass} and Johannesen, {Helle Hjorth} and Becker, {J{\"u}rgen C} and Pedersen, {Katrine S.} and Christine Dethlefsen and Jens Nielsen and Julie Gehl and Pedersen, {Bente Klarlund} and Straten, {Per Thor} and Pernille H{\o}jman",

year = "2016",

month = mar,

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doi = "10.1016/j.cmet.2016.01.011",

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journal = "Cell Metabolism",

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T1 - Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution

AU - Pedersen, Line

AU - Idorn, Manja

AU - Olofsson, Gitte H.

AU - Lauenborg, Britt

AU - Nookaew, Intawat

AU - Hansen, Rasmus Hvass

AU - Johannesen, Helle Hjorth

AU - Becker, Jürgen C

AU - Pedersen, Katrine S.

AU - Dethlefsen, Christine

AU - Nielsen, Jens

AU - Gehl, Julie

AU - Pedersen, Bente Klarlund

AU - Straten, Per Thor

AU - Højman, Pernille

PY - 2016/3/8

Y1 - 2016/3/8

N2 - 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 upregulation 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 β-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.

AB - 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 upregulation 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 β-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.

U2 - 10.1016/j.cmet.2016.01.011

DO - 10.1016/j.cmet.2016.01.011

M3 - Letter

C2 - 26895752

SN - 1550-4131

VL - 23

SP - 554

EP - 562

JO - Cell Metabolism

JF - Cell Metabolism

IS - 3

ER -

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

Abstract

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