title: Ethanol-induced mast cell-mediated inflammation leads to increased susceptibility of intestinal tumorigenesis in the APC Δ468 min mouse model of colon cancer.
abstract: BACKGROUND
  Chronic and frequent alcohol (ethanol [EtOH]) intake has been associated with an increased incidence of several types of cancers including breast, mouth, throat, esophageal, stomach, and colorectal (CRC). The underlying mechanism of this deleterious carcinogenic effect of alcohol has not been clearly established but inflammation may be 1 unifying feature of these cancers. We have recently shown that intestinal mast cells play a central role in intestinal carcinogenesis. In this study, we tested our hypothesis that mast cell-mediated inflammation is 1 underlying mechanism by which chronic alcohol promotes intestinal tumorigenesis.
  
  
  METHODS
  APC(Δ468) mice were fed either an alcohol-containing Nanji liquid diet or isocaloric dextrose-containing Nanji diet for 10 weeks and then sacrificed to collect small and large intestine samples. Assessments of tumor number and size as well as mast cell number and mast cell activity and histology score for invasion were compared between Control (dextrose-fed) and alcohol-fed APC(∆468) mice. The effect of alcohol on mast cell-mediated tumor migration was also assessed using an in vitro migration assay.
  
  
  RESULTS
  Alcohol feeding increased both polyp number and size within both the small and the large intestines of APC(∆468) mice. Only alcohol-fed mice showed evidence of tumor invasion. Chronic alcohol feeding also resulted in an increased mast cell number and activity in tumor stroma and invading borders. In vitro migration assay showed that alcohol significantly increases mast cell-mediated tumor migration in vitro.
  
  
  CONCLUSIONS
  Our data show that chronic alcohol intake promotes: (i) intestinal tumorigenesis and tumor invasion in genetically susceptible mice; (ii) increases in polyp-associated mast cells; and (iii) mast cell-mediated tumor migration in vitro. Both our in vivo and in vitro studies suggest that mast cell-mediated inflammation could be 1 mechanism by which alcohol promotes carcinogenesis.
authors: Department of Pharmacology, Rush University, Chicago, Illinois 60612, USA.
authors: Andre L
authors: AL
authors: Wimberly
authors: Christopher B
authors: CB
authors: Forsyth
authors: Mohammad W
authors: MW
authors: Khan
authors: Alan
authors: A
authors: Pemberton
authors: Khashayarsha
authors: K
authors: Khazaie
authors: Ali
authors: A
authors: Keshavarzian
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness / Q000276:immunology / Q000473:pathology; D011897:Random Allocation
chemical_list: D000431:Ethanol; D005947:Glucose