Exercise-Mediated Lowering of Glutamine Availability Suppresses Tumor Growth and Attenuates Muscle Wasting

Katrine S Pedersen; Francesco Gatto; Bo Zerahn; Jens Nielsen; Bente K Pedersen; Pernille Hojman; Julie Gehl

doi:10.1016/j.isci.2020.100978

Exercise-Mediated Lowering of Glutamine Availability Suppresses Tumor Growth and Attenuates Muscle Wasting

iScience. 2020 Apr 24;23(4):100978. doi: 10.1016/j.isci.2020.100978. Epub 2020 Mar 12.

Authors

Katrine S Pedersen¹, Francesco Gatto², Bo Zerahn³, Jens Nielsen⁴, Bente K Pedersen¹, Pernille Hojman¹, Julie Gehl⁵

Affiliations

¹ The Centre for Physical Activity Research (CFAS) and Centre of Inflammation and Metabolism (CIM), Copenhagen University Hospital, University of Copenhagen, 7641, 2200 Copenhagen, Denmark.
² Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Göteborg, Sweden; Elypta AB, Stockholm, Sweden.
³ Department of Clinical Physiology and Nuclear Medicine, Herlev and Gentofte University Hospital, 2730 Herlev, Denmark.
⁴ Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Göteborg, Sweden.
⁵ Center for Experimental Drug and Gene Electrotransfer (C∗EDGE), Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Sygehusvej 10, 4000 Roskilde, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, 2730 Herlev, Denmark. Electronic address: kgeh@regionsjaelland.dk.

Abstract

Glutamine is a central nutrient for many cancers, contributing to the generation of building blocks and energy-promoting signaling necessary for neoplastic proliferation. In this study, we hypothesized that lowering systemic glutamine levels by exercise may starve tumors, thereby contributing to the inhibitory effect of exercise on tumor growth. We demonstrate that limiting glutamine availability, either pharmacologically or physiologically by voluntary wheel running, significantly attenuated the growth of two syngeneic murine tumor models of breast cancer and lung cancer, respectively, and decreased markers of atrophic signaling in muscles from tumor-bearing mice. In continuation, wheel running completely abolished tumor-induced loss of weight and lean body mass, independently of the effect of wheel running on tumor growth. Moreover, wheel running abolished tumor-induced upregulation of muscular glutamine transporters and myostatin signaling. In conclusion, our data suggest that voluntary wheel running preserves muscle mass by counteracting muscular glutamine release and tumor-induced atrophic signaling.

Keywords: Cancer; Physiology; Specialized Functions of Cells.