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 K. Pedersen, Per Thor Straten, Pernille Hojman

    Publikation: Bidrag til tidsskriftArtikelForskningpeer review

    Abstrakt

    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.

    OriginalsprogEngelsk
    Sider (fra-til)554-562
    Antal sider9
    TidsskriftCell Metabolism
    Vol/bind23
    Udgave nummer3
    DOI
    StatusUdgivet - 8 mar. 2016

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