title: The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia.
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.
authors.affiliation: Department of Surgery, Simon Cancer Center and IUPUI Center for Cachexia Research, Innovation and Therapy, Indiana University School of Medicine.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bonetto
authors.affiliation: Department of Surgery, Simon Cancer Center and IUPUI Center for Cachexia Research, Innovation and Therapy, Indiana University School of Medicine.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Rupert
authors.affiliation: Department of Surgery, Simon Cancer Center and IUPUI Center for Cachexia Research, Innovation and Therapy, Indiana University School of Medicine.
authors.forename: Rafael
authors.initials: R
authors.lastname: Barreto
authors.affiliation: Department of Surgery, Simon Cancer Center and IUPUI Center for Cachexia Research, Innovation and Therapy, Indiana University School of Medicine; zimmerst@iu.edu.
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Zimmers
mesh_terms: D000818:Animals; D002100:Cachexia / Q000209:etiology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D004195:Disease Models, Animal; D006801:Humans; D015850:Interleukin-6; D051379:Mice; D018482:Muscle, Skeletal; D009133:Muscular Atrophy / Q000209:etiology; D015203:Reproducibility of Results
chemical_list: D015850:Interleukin-6