Gut barrier dysfunction in the ApcMin/+ mouse model of colon cancer cachexia

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1812

Article

Baynes, John W.²  Carson, James A.^1,2 

[1] Univ S Carolina, Dept Exercise Sci, Publ Hlth Res Ctr, Integrat Muscle Biol Lab, Columbia, SC 29208 USA

[2] Univ S Carolina, Ctr Colon Canc Res, Columbia, SC 29208 USA

关键词: Cachexia;    Colorectal cancer;    Endotoxin;    Gut barrier dysfunction;    Gut permeability;    Inflammation;   

DOI  :  10.1016/j.bbadis.2011.08.010

来源: Elsevier

【 摘 要 】

Background: The Apc(Min/+) mouse, an animal model of colorectal cancer and cachexia, has a heterologous mutation in the Apc tumor suppressor gene, predisposing the mouse to intestinal and colon tumor development. This mouse develops intestinal polyps by similar to 4 weeks of age, and loses body weight gradually between similar to 14 and similar to 20 weeks of age. The strengths of this cachexia model derive from several features that mimic human cancer, including a gradual increase in tumor burden, chronic inflammation, and anemia. Little is known about the role of gut barrier dysfunction and endotoxemia in the development of cancer cachexia. We sought to determine how gut permeability and resultant endotoxemia change with the progression of cachexia. Methods: Intestinal gut barrier integrity was assessed by permeability to FITC-dextran (MWav = 4000 kDa; FD4). Plasma glucose and triglycerides were measured by enzymatic assays, IL-6 by enzyme-linked immunosorbent assay, and endotoxin by the limulus amoebocyte assay. Body temperature was measured using a rectal probe. Results: Progression of cachexia was accompanied by development of gut barrier dysfunction (permeability to FD4), hypertrophy of mesenteric lymph nodes, and an increase in plasma endotoxin concentration. Changes in blood glucose and glucose tolerance, plasma IL-6, triglycerides, and body temperature were characteristic of endotoxemia. Conclusion: We propose a role for gut barrier dysfunction (GBD) and subsequent endotoxemia in the development of inflammation and progression of cachexia in the Apc(Min/+) mouse. (C) 2011 Elsevier B.V. All rights reserved.

【 授权许可】

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