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Physical activity modulates mononuclear phagocytes in mammary tissue and inhibits tumor growth in mice

The risk for breast cancer is significantly reduced in persons who engage in greater amounts of physical activity, and greater physical activity before or after diagnosis associates with reduced disease-specific mortality. Previous mechanistic studies indicate that components of innate immunity can...

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Autores principales: Lamkin, Donald M., Bradshaw, Karen P., Chang, Janice, Epstein, Ma’ayan, Gomberg, Jack, Prajapati, Krupa P., Soliman, Veronica H., Sylviana, Thezia, Wong, Yinnie, Morizono, Kouki, Sloan, Erica K., Cole, Steve W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821756/
https://www.ncbi.nlm.nih.gov/pubmed/33552733
http://dx.doi.org/10.7717/peerj.10725
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author Lamkin, Donald M.
Bradshaw, Karen P.
Chang, Janice
Epstein, Ma’ayan
Gomberg, Jack
Prajapati, Krupa P.
Soliman, Veronica H.
Sylviana, Thezia
Wong, Yinnie
Morizono, Kouki
Sloan, Erica K.
Cole, Steve W.
author_facet Lamkin, Donald M.
Bradshaw, Karen P.
Chang, Janice
Epstein, Ma’ayan
Gomberg, Jack
Prajapati, Krupa P.
Soliman, Veronica H.
Sylviana, Thezia
Wong, Yinnie
Morizono, Kouki
Sloan, Erica K.
Cole, Steve W.
author_sort Lamkin, Donald M.
collection PubMed
description The risk for breast cancer is significantly reduced in persons who engage in greater amounts of physical activity, and greater physical activity before or after diagnosis associates with reduced disease-specific mortality. Previous mechanistic studies indicate that components of innate immunity can mediate an inhibitory effect of physical activity on several types of tumor. However, in breast cancer specifically, the myeloid compartment of innate immunity is thought to exhibit high propensity for an immunosuppressive role that obstructs anti-tumor immunity. Thus, we tested the notion that greater physical activity alters mononuclear phagocytes in mammary tissue when inhibiting nascent tumor in a murine model of breast cancer. To model greater physical activity, we placed an angled running wheel in each mouse’s home cage for two weeks before tumor engraftment with EO771 mammary cancer cells that express luciferase for bioluminescent detection. Fully immunocompetent mice and mice with compromised adaptive immunity showed significantly less mammary tumor signal when given access to running wheels, although the effect size was smaller in this latter group. To investigate the role of the myeloid compartment, mononuclear phagocytes were ablated by systemic injection of clodronate liposomes at 24 h before tumor engraftment and again at the time of tumor engraftment, and this treatment reversed the inhibition in wheel running mice. However, clodronate also inhibited mammary tumor signal in sedentary mice, in conjunction with an expected decrease in gene and protein expression of the myeloid antigen, F4/80 (Adgre1), in mammary tissue. Whole transcriptome digital cytometry with CIBERSORTx was used to analyze myeloid cell populations in mammary tissue following voluntary wheel running and clodronate treatment, and this approach found significant changes in macrophage and monocyte populations. In exploratory analyses, whole transcriptome composite scores for monocytic myeloid-derived suppressor cell (M-MDSC), macrophage lactate timer, and inflammation resolution gene expression programs were significantly altered. Altogether, the results support the hypothesis that physical activity inhibits nascent mammary tumor growth by enhancing the anti-tumor potential of mononuclear phagocytes in mammary tissue.
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spelling pubmed-78217562021-02-04 Physical activity modulates mononuclear phagocytes in mammary tissue and inhibits tumor growth in mice Lamkin, Donald M. Bradshaw, Karen P. Chang, Janice Epstein, Ma’ayan Gomberg, Jack Prajapati, Krupa P. Soliman, Veronica H. Sylviana, Thezia Wong, Yinnie Morizono, Kouki Sloan, Erica K. Cole, Steve W. PeerJ Animal Behavior The risk for breast cancer is significantly reduced in persons who engage in greater amounts of physical activity, and greater physical activity before or after diagnosis associates with reduced disease-specific mortality. Previous mechanistic studies indicate that components of innate immunity can mediate an inhibitory effect of physical activity on several types of tumor. However, in breast cancer specifically, the myeloid compartment of innate immunity is thought to exhibit high propensity for an immunosuppressive role that obstructs anti-tumor immunity. Thus, we tested the notion that greater physical activity alters mononuclear phagocytes in mammary tissue when inhibiting nascent tumor in a murine model of breast cancer. To model greater physical activity, we placed an angled running wheel in each mouse’s home cage for two weeks before tumor engraftment with EO771 mammary cancer cells that express luciferase for bioluminescent detection. Fully immunocompetent mice and mice with compromised adaptive immunity showed significantly less mammary tumor signal when given access to running wheels, although the effect size was smaller in this latter group. To investigate the role of the myeloid compartment, mononuclear phagocytes were ablated by systemic injection of clodronate liposomes at 24 h before tumor engraftment and again at the time of tumor engraftment, and this treatment reversed the inhibition in wheel running mice. However, clodronate also inhibited mammary tumor signal in sedentary mice, in conjunction with an expected decrease in gene and protein expression of the myeloid antigen, F4/80 (Adgre1), in mammary tissue. Whole transcriptome digital cytometry with CIBERSORTx was used to analyze myeloid cell populations in mammary tissue following voluntary wheel running and clodronate treatment, and this approach found significant changes in macrophage and monocyte populations. In exploratory analyses, whole transcriptome composite scores for monocytic myeloid-derived suppressor cell (M-MDSC), macrophage lactate timer, and inflammation resolution gene expression programs were significantly altered. Altogether, the results support the hypothesis that physical activity inhibits nascent mammary tumor growth by enhancing the anti-tumor potential of mononuclear phagocytes in mammary tissue. PeerJ Inc. 2021-01-19 /pmc/articles/PMC7821756/ /pubmed/33552733 http://dx.doi.org/10.7717/peerj.10725 Text en ©2021 Lamkin 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, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Animal Behavior
Lamkin, Donald M.
Bradshaw, Karen P.
Chang, Janice
Epstein, Ma’ayan
Gomberg, Jack
Prajapati, Krupa P.
Soliman, Veronica H.
Sylviana, Thezia
Wong, Yinnie
Morizono, Kouki
Sloan, Erica K.
Cole, Steve W.
Physical activity modulates mononuclear phagocytes in mammary tissue and inhibits tumor growth in mice
title Physical activity modulates mononuclear phagocytes in mammary tissue and inhibits tumor growth in mice
title_full Physical activity modulates mononuclear phagocytes in mammary tissue and inhibits tumor growth in mice
title_fullStr Physical activity modulates mononuclear phagocytes in mammary tissue and inhibits tumor growth in mice
title_full_unstemmed Physical activity modulates mononuclear phagocytes in mammary tissue and inhibits tumor growth in mice
title_short Physical activity modulates mononuclear phagocytes in mammary tissue and inhibits tumor growth in mice
title_sort physical activity modulates mononuclear phagocytes in mammary tissue and inhibits tumor growth in mice
topic Animal Behavior
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821756/
https://www.ncbi.nlm.nih.gov/pubmed/33552733
http://dx.doi.org/10.7717/peerj.10725
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