title: Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse.
abstract: BACKGROUND
  The majority of cancer patients experience dramatic weight loss, due to cachexia and consisting of skeletal muscle and fat tissue wasting. Cachexia is a negative prognostic factor, interferes with therapy and worsens the patients' quality of life by affecting muscle function. Mice bearing ectopically-implanted C26 colon carcinoma are widely used as an experimental model of cancer cachexia. As part of the search for novel clinical and basic research applications for this experimental model, we characterized novel cellular and molecular features of C26-bearing mice.
  
  
  METHODS
  A fragment of C26 tumor was subcutaneously grafted in isogenic BALB/c mice. The mass growth and proliferation rate of the tumor were analyzed. Histological and cytofluorometric analyses were used to assess cell death, ploidy and differentiation of the tumor cells. The main features of skeletal muscle atrophy, which were highlighted by immunohistochemical and electron microscopy analyses, correlated with biochemical alterations. Muscle force and resistance to fatigue were measured and analyzed as major functional deficits of the cachectic musculature.
  
  
  RESULTS
  We found that the C26 tumor, ectopically implanted in mice, is an undifferentiated carcinoma, which should be referred to as such and not as adenocarcinoma, a common misconception. The C26 tumor displays aneuploidy and histological features typical of transformed cells, incorporates BrdU and induces severe weight loss in the host, which is largely caused by muscle wasting. The latter appears to be due to proteasome-mediated protein degradation, which disrupts the sarcomeric structure and muscle fiber-extracellular matrix interactions. A pivotal functional deficit of cachectic muscle consists in increased fatigability, while the reported loss of tetanic force is not statistically significant following normalization for decreased muscle fiber size.
  
  
  CONCLUSIONS
  We conclude, on the basis of the definition of cachexia, that ectopically-implanted C26 carcinoma represents a well standardized experimental model for research on cancer cachexia. We wish to point out that scientists using the C26 model to study cancer and those using the same model to study cachexia may be unaware of each other's works because they use different keywords; we present strategies to eliminate this gap and discuss the benefits of such an exchange of knowledge.
authors.affiliation: Department of Histology and Medical Embryology, Sapienza University of Rome, Via Scarpa 16, 00161 Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Aulino
authors.forename: Emanuele
authors.initials: E
authors.lastname: Berardi
authors.forename: Veronica M
authors.initials: VM
authors.lastname: Cardillo
authors.forename: Emanuele
authors.initials: E
authors.lastname: Rizzuto
authors.forename: Barbara
authors.initials: B
authors.lastname: Perniconi
authors.forename: Carla
authors.initials: C
authors.lastname: Ramina
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Padula
authors.forename: Enrico P
authors.initials: EP
authors.lastname: Spugnini
authors.forename: Alfonso
authors.initials: A
authors.lastname: Baldi
authors.forename: Fabio
authors.initials: F
authors.lastname: Faiola
authors.forename: Sergio
authors.initials: S
authors.lastname: Adamo
authors.forename: Dario
authors.initials: D
authors.lastname: Coletti
mesh_terms: D000230:Adenocarcinoma / Q000150:complications* / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002100:Cachexia / Q000209:etiology* / Q000473:pathology; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000150:complications* / Q000473:pathology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000150:complications* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000473:pathology*; D009133:Muscular Atrophy / Q000209:etiology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger