TY - JOUR

T1 - Exercise-Mediated Lowering of Glutamine Availability Suppresses Tumor Growth and Attenuates Muscle Wasting

AU - Pedersen, Katrine S.

AU - Gatto, Francesco

AU - Zerahn, Bo

AU - Nielsen, Jens

AU - Pedersen, Bente K.

AU - Hojman, Pernille

AU - Gehl, Julie

PY - 2020/4

Y1 - 2020/4

N2 - 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.

AB - 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.

KW - Cancer

KW - Physiology

KW - Specialized Functions of Cells

U2 - 10.1016/j.isci.2020.100978

DO - 10.1016/j.isci.2020.100978

M3 - Journal article

C2 - 32240949

AN - SCOPUS:85082412265

VL - 23

JO - iScience

JF - iScience

SN - 2589-0042

IS - 4

M1 - 100978

ER -