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Updated: Jul 29, 2025
The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia
Published on: November 30, 2016
Decreased insulin-like growth factor-1 expression in response to mechanical loading is associated with skeletal
Mitsunori Miyazaki1, Atsushi Sawada2, Daisuke Sawamura3
1Department of Integrative Physiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan; Department of Physical Therapy, School of Rehabilitation Sciences, Health Sciences University of Hokkaido, Japan.
Objective:
Cachexia is a systemic metabolic syndrome characterized by loss of body weight and skeletal muscle mass during chronic wasting diseases, such as cancer. Skeletal muscle in cancer cachexia is less responsive to anabolic factors including mechanical loading; however, the precise molecular mechanism is largely unknown. In this study, we examined the underlying mechanism of anabolic resistance in skeletal muscle in a cancer cachexia model.
Methods:
CD2F1 mice (male, 8 weeks old) were subcutaneously transplanted (1 × 106 cells per mouse) with a mouse colon cancer-derived cell line (C26) as a model of cancer cachexia. Mechanical overload of the plantaris muscle by synergist tenotomy was performed during the 2nd week and the plantaris muscle was sampled at the 4th week following C26 transplantation.
Results:
The hypertrophic response of skeletal muscle (increased skeletal muscle weight/protein synthesis efficiency and activation of mechanistic target of rapamycin complex 1 signaling) associated with mechanical overload was significantly suppressed during cancer cachexia. Screening of gene expression profile and pathway analysis using microarray revealed that blunted muscle protein synthesis was associated with cancer cachexia and was likely induced by downregulation of insulin-like growth factor-1 (IGF-1) and impaired activation of IGF-1-dependent signaling.
Conclusions:
These observations indicate that cancer cachexia induces resistance to muscle protein synthesis, which may be a factor for inhibiting the anabolic adaptation of skeletal muscle to physical exercise in cancer patients.
Insights
Cancer cachexia causes anabolic resistance in skeletal muscle, impairing muscle growth and protein synthesis. This resistance is linked to reduced insulin-like growth factor-1 (IGF-1) signaling, hindering exercise adaptation in cancer patients.
Area of Science:
- Biomedical Science
- Molecular Biology
- Exercise Physiology
Background:
- Cachexia is a metabolic syndrome causing significant weight and muscle loss in chronic diseases like cancer.
- Skeletal muscle in cancer cachexia exhibits reduced responsiveness to anabolic stimuli, such as mechanical loading, with unclear molecular mechanisms.
- Understanding this anabolic resistance is crucial for developing interventions to preserve muscle mass in cancer patients.
Purpose of the Study:
- To investigate the molecular mechanisms underlying anabolic resistance in skeletal muscle within a cancer cachexia model.
- To determine how cancer cachexia affects the skeletal muscle's response to mechanical overload.
- To identify key molecular pathways involved in impaired muscle protein synthesis during cancer cachexia.
Main Methods:
- A mouse model of cancer cachexia was established using C26 colon cancer cells in CD2F1 mice.
- Mechanical overload was induced via synergist tenotomy of the plantaris muscle.
- Gene expression profiling and pathway analysis were performed on muscle samples.
Main Results:
- Cancer cachexia significantly suppressed the hypertrophic response of skeletal muscle to mechanical overload.
- Muscle protein synthesis efficiency and mechanistic target of rapamycin complex 1 (mTORC1) signaling were blunted.
- Gene expression analysis revealed downregulation of insulin-like growth factor-1 (IGF-1) and impaired IGF-1-dependent signaling pathways.
Conclusions:
- Cancer cachexia induces resistance to muscle protein synthesis, contributing to anabolic resistance.
- Impaired IGF-1 signaling is a key molecular mechanism behind this resistance.
- These findings suggest a reason for the limited anabolic adaptation to exercise in cancer patients.
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