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Role of gut barrier dysfunction and endotoxemia in development of colon cancer cachexia
Author(s) -
Puppa Melissa J,
White James P,
Sato Shuichi,
Baynes John W,
Carson James A
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1005.2
Subject(s) - colorectal cancer , cachexia , medicine , cancer , endocrinology , intestinal permeability
Cachexia, accounts for ~30% of all cancer‐related deaths, and up to 50% of deaths in patients with gastrointestinal cancers. Apc Min/+ mice have been used as a model of colorectal cancer that become cachetic at 4–5 months of age. Gut barrier dysfunction (GBD) is an increase in the permeability of intestinal epithelium which can allow bacteria to breach the gut barrier and induce an inflammatory response. The purpose of this study was to determine if GBD is associated with cachexia in the Apc Min/+ mouse. Mice were administered FITC‐dextran, FD4, (MW 4000 Da) by gavage and blood sampled 1h later via retraorbital stick. Plasma endotoxin was measured with the limulus assay at 12wk and 19wk of age. There was a 27% decrease in body weight of the Apc Min/+ mice at 20 wks compared to the C57/BL6 wild type. Plasma FD4 was increased in the Apc Min/+ mice at 20wk compared to 14wks (6.9±2.4 μg/ml, n=10 vs 0.5±.5μg/ml, n=7). Endotoxin was greater at 19wks than 12wk Apc Min/+ mice (10.5±3EU/ml, n=9 vs 2.02±.8EU/ml, n=4). Mesentaric lymphs were taken at the 20wks were significantly larger in the Apc Min/+ mice compared with wild type mice (38±2.4mg, n=6 vs 24.4±1.7mg, n=9). Tumor number between 12 and 20 weeks was not different but, 20wk Apc Min/+ mice had an 8 fold greater number of large tumors. From these results, we hypothesize that GBD and resultant endotoxemia induce the pro‐inflammatory state that leads to development of cachexia in ApcMin/+ mice.