The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia

Andrea Bonetto, Joseph E. Rupert, Rafael Barreto, Teresa Zimmers

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Cancer cachexia is the progressive loss of skeletal muscle mass and adipose tissue, negative nitrogen balance, anorexia, fatigue, inflammation, and activation of lipolysis and proteolysis systems. Cancer patients with cachexia benefit less from anti-neoplastic therapies and show increased mortality1. Several animal models have been established in order to investigate the molecular causes responsible for body and muscle wasting as a result of tumor growth. Here, we describe methodologies pertaining to a well-characterized model of cancer cachexia: mice bearing the C26 carcinoma2-4. Although this model is heavily used in cachexia research, different approaches make reproducibility a potential issue. The growth of the C26 tumor causes a marked and progressive loss of body and skeletal muscle mass, accompanied by reduced muscle cross-sectional area and muscle strength3-5. Adipose tissue is also lost. Wasting is coincident with elevated circulating levels of pro-inflammatory cytokines, particularly Interleukin-6 (IL-6)3, which is directly, although not entirely, responsible for C26 cachexia. It is well-accepted that a primary mechanism by which the C26 tumor induces muscle tissue depletion is the activation of skeletal muscle proteolytic systems. Thus, expression of muscle-specific ubiquitin ligases, such as atrogin-1/MAFbx and MuRF-1, represent an accepted method for the evaluation of the ongoing muscle catabolism2. Here, we present how to execute this model in a reproducible manner and how to excise several tissues and organs (the liver, spleen, and heart), as well as fat and skeletal muscles (the gastrocnemius, tibialis anterior, and quadriceps). We also provide useful protocols that describe how to perform muscle freezing, sectioning, and fiber size quantification.

Original languageEnglish (US)
JournalJournal of visualized experiments : JoVE
Issue number117
DOIs
StatePublished - Nov 30 2016

Fingerprint

Bearings (structural)
Cachexia
Muscle
Tumors
Colon
Carcinoma
Muscles
Neoplasms
Skeletal Muscle
Tissue
Adipose Tissue
Interleukin-3
Lipolysis
Chemical activation
Anorexia
Ligases
Growth
Ubiquitin
Proteolysis
Freezing

ASJC Scopus subject areas

  • Neuroscience(all)
  • Chemical Engineering(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia. / Bonetto, Andrea; Rupert, Joseph E.; Barreto, Rafael; Zimmers, Teresa.

In: Journal of visualized experiments : JoVE, No. 117, 30.11.2016.

Research output: Contribution to journalArticle

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