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. 2022 Oct 21:13:1033585.
doi: 10.3389/fphys.2022.1033585. eCollection 2022.

Myokines derived from contracting skeletal muscle suppress anabolism in MCF7 breast cancer cells by inhibiting mTOR

Amanda R Davis  1 , Chelsea G Goodenough  1 , Kim C Westerlind  2 , Robert Strange  2 , John W Deaver  1 , Patrick J Ryan  1 , Steven E Riechman  1 , James D Fluckey  1
Affiliations

Myokines derived from contracting skeletal muscle suppress anabolism in MCF7 breast cancer cells by inhibiting mTOR

Amanda R Davis et al. Front Physiol. .

Abstract

There is strong evidence that physical activity has a profound protective effect against multiple types of cancer. Here, we show that this effect may be mediated by factors released from skeletal muscle during simulated exercise, in situ, which suppress canonical anabolic signaling in breast cancer. We report attenuated growth of MCF7 breast cancer cells in the presence of a rodent-derived exercise conditioned perfusate, independent of prior exercise training. This reduction was concomitant with increased levels of DEPTOR protein and reduced mTOR activity.

Keywords: cell culture; electrical stimulation; myokines; protein synthesis; tumor suppression.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
E-Stim perfusate suppresses tumor growth. Treatment with E-Stim perfusate resulted in reductions in both cell counts in vitro (A) and tumor volume in vivo (B) when compared to the Non-Stim condition. ** denotes p < 0.01, **** denotes p < 0.0001.
FIGURE 2
FIGURE 2
E-Stim perfusate suppresses anabolic signaling in MCF7 breast cancer cells. Cellular protein fractional synthesis rate was reduced by E-Stim perfusate treatment (A). E-Stim perfusate also lead to an accumulation of the endogenous mTOR inhibitor DEPTOR (B), concomitant with reduced signaling through the downstream targets of the anabolic mTOR kinase (C,D). * denotes p < 0.05, ** denotes p < 0.01.
FIGURE 3
FIGURE 3
Habitual exercise does not alter the effect of E-Stim perfusate on breast cancer cell growth. E-Stim perfusates gathered from both trained and untrained animals led to similar reductions in MCF7 cell count. * denotes p < 0.05, ** denotes p < 0.01.
FIGURE 4
FIGURE 4
Albumin is required to mediate the chemotherapeutic effects of E-Stim perfusate. In perfusates where albumin (A−C) was substituted with dextran (D−F), no effect of E-Stim perfusate treatment on MCF7 cell count was observed. The purpose of this experiment was to determine if albumin in the perfusate had a role in delivering myokines through the vasculature. * denotes p < 0.05, ** denotes p < 0.01.
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References

    1. Alinovskaya L. I., Sedykh S. E., Ivanisenko N. V., Soboleva S. E., Nevinsky G. A. (2018). How human serum albumin recognizes DNA and RNA. Biol. Chem. 399, 347–360. 10.1515/hsz-2017-0243 - DOI - PubMed
    1. Aoi W., Naito Y., Takagi T., Tanimura Y., Takanami Y., Kawai Y., et al. (2013). A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise. Gut 62, 882–889. 10.1136/gutjnl-2011-300776 - DOI - PubMed
    1. Arroyo J. D., Chevillet J. R., Kroh E. M., Ruf I. K., Pritchard C. C., Gibson D. F., et al. (2011). Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc. Natl. Acad. Sci. U. S. A. 108, 5003–5008. 10.1073/pnas.1019055108 - DOI - PMC - PubMed
    1. Baselga J., Campone M., Piccart M., Burris H. A., Rugo H. S., Sahmoud T., et al. (2012). Everolimus in postmenopausal hormone-receptor–positive advanced breast cancer. N. Engl. J. Med. 366, 520–529. 10.1056/NEJMoa1109653 - DOI - PMC - PubMed
    1. Basho R. K., Yam C., Gilcrease M., Murthy R. K., Helgason T., Karp D. D., et al. (2018). Comparative effectiveness of an mTOR‐based systemic therapy regimen in advanced, metaplastic and nonmetaplastic triple‐negative breast cancer. Oncologist 23, 1300–1309. 10.1634/theoncologist.2017-0498 - DOI - PMC - PubMed