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Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer
Cancer causes mitochondrial alterations in skeletal muscle, which may progress to muscle wasting and, ultimately, to cancer cachexia. Understanding how exercise adaptations are altered by cancer and cancer treatment is important for the effective design of exercise interventions aimed at improving c...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525738/ https://www.ncbi.nlm.nih.gov/pubmed/34665826 http://dx.doi.org/10.1371/journal.pone.0258831 |
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author | Buss, Linda A. Hock, Barry Merry, Troy L. Ang, Abel D. Robinson, Bridget A. Currie, Margaret J. Dachs, Gabi U. |
author_facet | Buss, Linda A. Hock, Barry Merry, Troy L. Ang, Abel D. Robinson, Bridget A. Currie, Margaret J. Dachs, Gabi U. |
author_sort | Buss, Linda A. |
collection | PubMed |
description | Cancer causes mitochondrial alterations in skeletal muscle, which may progress to muscle wasting and, ultimately, to cancer cachexia. Understanding how exercise adaptations are altered by cancer and cancer treatment is important for the effective design of exercise interventions aimed at improving cancer outcomes. We conducted an exploratory study to investigate how tumor burden and cancer immunotherapy treatment (anti-PD-1) modify the skeletal muscle mitochondrial response to exercise training in mice with transplantable tumors (B16-F10 melanoma and EO771 breast cancer). Mice remained sedentary or were provided with running wheels for ~19 days immediately following tumor implant while receiving no treatment (Untreated), isotype control antibody (IgG2a) or anti-PD-1. Exercise and anti-PD-1 did not alter the growth rate of either tumor type, either alone or in combination therapy. Untreated mice with B16-F10 tumors showed increases in most measured markers of skeletal muscle mitochondrial content following exercise training, as did anti-PD-1-treated mice, suggesting increased mitochondrial content following exercise training in these groups. However, mice with B16-F10 tumors receiving the isotype control antibody did not exhibit increased skeletal muscle mitochondrial content following exercise. In untreated mice with EO771 tumors, only citrate synthase activity and complex IV activity were increased following exercise. In contrast, IgG2a and anti-PD-1-treated groups both showed robust increases in most measured markers following exercise. These results indicate that in mice with B16-F10 tumors, IgG2a administration prevents exercise adaptation of skeletal muscle mitochondria, but adaptation remains intact in mice receiving anti-PD-1. In mice with EO771 tumors, both IgG2a and anti-PD-1-treated mice show robust skeletal muscle mitochondrial exercise responses, while untreated mice do not. Taken together, we postulate that immune modulation may enhance skeletal muscle mitochondrial response to exercise in tumor-bearing mice, and suggest this as an exciting new avenue for future research in exercise oncology. |
format | Online Article Text |
id | pubmed-8525738 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-85257382021-10-20 Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer Buss, Linda A. Hock, Barry Merry, Troy L. Ang, Abel D. Robinson, Bridget A. Currie, Margaret J. Dachs, Gabi U. PLoS One Research Article Cancer causes mitochondrial alterations in skeletal muscle, which may progress to muscle wasting and, ultimately, to cancer cachexia. Understanding how exercise adaptations are altered by cancer and cancer treatment is important for the effective design of exercise interventions aimed at improving cancer outcomes. We conducted an exploratory study to investigate how tumor burden and cancer immunotherapy treatment (anti-PD-1) modify the skeletal muscle mitochondrial response to exercise training in mice with transplantable tumors (B16-F10 melanoma and EO771 breast cancer). Mice remained sedentary or were provided with running wheels for ~19 days immediately following tumor implant while receiving no treatment (Untreated), isotype control antibody (IgG2a) or anti-PD-1. Exercise and anti-PD-1 did not alter the growth rate of either tumor type, either alone or in combination therapy. Untreated mice with B16-F10 tumors showed increases in most measured markers of skeletal muscle mitochondrial content following exercise training, as did anti-PD-1-treated mice, suggesting increased mitochondrial content following exercise training in these groups. However, mice with B16-F10 tumors receiving the isotype control antibody did not exhibit increased skeletal muscle mitochondrial content following exercise. In untreated mice with EO771 tumors, only citrate synthase activity and complex IV activity were increased following exercise. In contrast, IgG2a and anti-PD-1-treated groups both showed robust increases in most measured markers following exercise. These results indicate that in mice with B16-F10 tumors, IgG2a administration prevents exercise adaptation of skeletal muscle mitochondria, but adaptation remains intact in mice receiving anti-PD-1. In mice with EO771 tumors, both IgG2a and anti-PD-1-treated mice show robust skeletal muscle mitochondrial exercise responses, while untreated mice do not. Taken together, we postulate that immune modulation may enhance skeletal muscle mitochondrial response to exercise in tumor-bearing mice, and suggest this as an exciting new avenue for future research in exercise oncology. Public Library of Science 2021-10-19 /pmc/articles/PMC8525738/ /pubmed/34665826 http://dx.doi.org/10.1371/journal.pone.0258831 Text en © 2021 Buss et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Buss, Linda A. Hock, Barry Merry, Troy L. Ang, Abel D. Robinson, Bridget A. Currie, Margaret J. Dachs, Gabi U. Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer |
title | Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer |
title_full | Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer |
title_fullStr | Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer |
title_full_unstemmed | Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer |
title_short | Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer |
title_sort | effect of immune modulation on the skeletal muscle mitochondrial exercise response: an exploratory study in mice with cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525738/ https://www.ncbi.nlm.nih.gov/pubmed/34665826 http://dx.doi.org/10.1371/journal.pone.0258831 |
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