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

PeerJ

article

Donald M. Lamkin¹  Karen P. Bradshaw¹  Janice Chang¹  Ma’ayan Epstein¹  Jack Gomberg¹  Krupa P. Prajapati¹  Veronica H. Soliman¹  Thezia Sylviana¹  Yinnie Wong¹  Kouki Morizono⁵  Erica K. Sloan¹  Steve W. Cole¹ 

[1] Norman Cousins Center for PNI, Semel Institute for Neuroscience, University of California;Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine, University of California;Jonsson Comprehensive Cancer Center, University of California;Department of Neuroscience, Stanford University School of Medicine;Divison of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California;UCLA AIDS Institute, David Geffen School of Medicine, University of California;Monash Institute of Pharmaceutical Sciences, Monash University;Division of Cancer Surgery, Peter MacCallum Cancer Centre-Victorian Comprehensive Cancer Centre

关键词: Exercise oncology;    Voluntary wheel running;    Breast cancer;    Innate immunity;    Myeloid cells;    Tumor immunology;    Monocytes;    Macrophages;    Transcriptomics;   

DOI  :  10.7717/peerj.10725

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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.

【 授权许可】

CC BY