Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer
Autor: | Barry D. Hock, Linda A. Buss, Abel Damien Ang, Bridget A. Robinson, Margaret J. Currie, Troy L. Merry, Gabi U. Dachs |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Physiology
Cancer Treatment Melanoma Experimental Mitochondrion Biochemistry Mice Random Allocation Breast Tumors Medicine and Health Sciences Medicine Citrate synthase Wasting Musculoskeletal System Immune Checkpoint Inhibitors Energy-Producing Organelles Multidisciplinary biology Melanoma Muscles Mitochondria Exercise Therapy Gene Expression Regulation Neoplastic medicine.anatomical_structure Treatment Outcome Oncology Physiological Parameters Female Immunotherapy medicine.symptom Anatomy Cellular Structures and Organelles Research Article medicine.medical_specialty Science Citrate (si)-Synthase Bioenergetics Electron Transport Complex IV Breast cancer Immune system Malignant Tumors Complementary and Alternative Medicine Internal medicine Cell Line Tumor Physical Conditioning Animal Breast Cancer Animals Muscle Skeletal business.industry Body Weight Cancer Skeletal muscle Cancers and Neoplasms Biology and Life Sciences Mammary Neoplasms Experimental Cell Biology medicine.disease Mitochondria Muscle Endocrinology Skeletal Muscles Immunoglobulin G biology.protein business |
Zdroj: | PLoS ONE PLoS ONE, Vol 16, Iss 10, p e0258831 (2021) |
ISSN: | 1932-6203 |
Popis: | 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. |
Databáze: | OpenAIRE |
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