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

Melissa J. Puppa, James P. White, Shuichi Sato, Mark Cairns, John W. Baynes, James Carson

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

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 ~4weeks of age, and loses body weight gradually between ~14 and ~20weeks 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 (MW av=4000kDa; 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.

Original languageEnglish (US)
Pages (from-to)1601-1606
Number of pages6
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1812
Issue number12
DOIs
StatePublished - Dec 1 2011

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Cachexia
Colonic Neoplasms
Endotoxemia
Permeability
Body Temperature
Endotoxins
Interleukin-6
Triglycerides
Intestinal Polyps
Inflammation
Glucose
Horseshoe Crabs
Neoplasms
Enzyme Assays
Tumor Burden
Tumor Suppressor Genes
Hypertrophy
Blood Glucose
Anemia
Colorectal Neoplasms

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology

Cite this

Gut barrier dysfunction in the Apc Min/+ mouse model of colon cancer cachexia. / Puppa, Melissa J.; White, James P.; Sato, Shuichi; Cairns, Mark; Baynes, John W.; Carson, James.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1812, No. 12, 01.12.2011, p. 1601-1606.

Research output: Contribution to journalArticle

Puppa, Melissa J. ; White, James P. ; Sato, Shuichi ; Cairns, Mark ; Baynes, John W. ; Carson, James. / Gut barrier dysfunction in the Apc Min/+ mouse model of colon cancer cachexia. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2011 ; Vol. 1812, No. 12. pp. 1601-1606.
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