Antibody-Directed Myostatin Inhibition Enhances Muscle Mass and Function in Tumor-Bearing Mice
Open accessAbstract
Cancer cachexia describes the progressive skeletal muscle wasting and weakness in many cancer patients and accounts for >20% of cancer-related deaths. We tested the hypothesis that antibody-directed myostatin inhibition would attenuate the atrophy and loss of function in muscles of tumor-bearing mice. Twelve-week-old C57BL/6 mice received a subcutaneous injection of saline (control) or Lewis lung carcinoma (LLC) tumor cells. One week later, mice received either once weekly injections of saline (control, n = 12; LLC, n = 9) or a mouse chimera of anti-human myostatin antibody (PF-354, 10 mg·kg⁻¹·wk⁻¹, LLC+PF-354, n = 11) for 5 wk. Injection of LLC cells reduced muscle mass and maximum force of tibialis anterior (TA) muscles by 8-10% (P 0.05). Maximum specific (normalized) force of diaphragm muscle strips was reduced with LLC injection (P 0.05). PF-354 enhanced activity of oxidative enzymes in TA and diaphragm muscles of tumor-bearing mice by 118% and 89%, respectively (P 0.05). Antibody-directed myostatin inhibition attenuated the skeletal muscle atrophy and loss of muscle force-producing capacity in a murine model of cancer cachexia, in part by reducing apoptosis. The improvements in limb muscle mass and function highlight the therapeutic potential of antibody-directed myostatin inhibition for cancer cachexia.
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A recent clinical trial using a monoclonal antibody blocking the myostatin receptor has not shown potent results in treating skeletal muscle wasting for COPD patients, despite promising results previously obtained in cancer models.
“However, a recent clinical trial using a monoclonal antibody blocking its receptor has not shown potent results in treating skeletal muscle wasting for COPD patients [177], despite promising results previously obtained in cancer models [178].”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [178]
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- Authors
- Murphy, K. T., Chee, A., Gleeson, B. G., Naim, T., Swiderski, K., Koopman, R., & Lynch, G. S.
- Affiliations
- The University of Melbourne (AU)
- Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Victoria, Australia
- Corresponding author
- Lynch, Gordon S.
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2011-09
- Volume
- 301
- Issue
- 3
- Pages
- R716-R726
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2052003759
- Cited by
- 111
- References
- 4
- Citations by year
- 2025: 2 · 2023: 7 · 2022: 9 · 2021: 8 · 2020: 9 · 2019: 3 · 2018: 12 · 2017: 11 · 2016: 10 · 2015: 9 · 2014: 6 · 2013: 15 · 2012: 10
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- cc-by
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- cancer cachexia, myostatin inhibition, skeletal muscle atrophy, muscle weakness, Lewis lung carcinoma, tibialis anterior, diaphragm, oxidative enzyme activity, apoptosis, muscle mass, muscle function
- MeSH terms
- Analysis of Variance, Animals, Antibodies, Cachexia, Energy Metabolism, Male, Mice, Inbred C57BL, Muscular Atrophy, Oxidation-Reduction, Phosphorylation, Succinate Dehydrogenase, Time Factors, Apoptosis, Muscle, Skeletal, Carcinoma, Lewis Lung, Muscle Weakness, Cell Proliferation, Mice, Smad3 Protein, Muscle Strength, Myostatin
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