Increased expression and possible role of chitinase 3-like-1 in a colitis-associated carcinoma model

World J Gastroenterol. 2014 Nov 14;20(42):15736-44. doi: 10.3748/wjg.v20.i42.15736.


Aim: To investigate the possible role of chitinase 3-like-1 (CHI3L1) in the progression of colitis-associated carcinoma (CAC).

Methods: Thirty-four Balb/c mice were randomly assigned to five groups, including the control, CAC control, CAC + caffeine, colitis control and colitis + caffeine. Three animals were sacrificed every two weeks for blinded macroscopic inspection, histological analysis, and total RNA extraction. An immunofluorescent assay was performed using specimens from the colitis control and colitis + caffeine groups to investigate whether the protective effect of caffeine was associated with less oxidative DNA damage. In vitro, HT29 cells pre-stimulated with different concentrations of recombinant CHI3L1 protein and H2O2 were loaded with the DCFH-DA fluorescent probe to determine the effect of CHI3L1 on intracellular reactive oxygen species production.

Results: CHI3L1 mRNA was increased during the progression of colon carcinogenesis. Tumors were mostly located in the distal end of the colon where the expression of CHI3L1 was higher than in the proximal colon. Caffeine-treated mice developed fewer tumors and milder inflammation than untreated mice. CHI3L1 protein increased reactive oxygen species in HT29 cells when exposed to H2O2.

Conclusion: Caffeine reduces tumor incidence by decreasing oxidative DNA damage. CHI3L1 may contribute to CAC by increasing reactive oxygen species production.

Keywords: Chitinase 3-like-1; Colitis-associated carcinoma; Colorectal cancer; Inflammatory bowel disease; Murine model; Oxidative stress; Ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / genetics
  • Adipokines / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anticarcinogenic Agents / pharmacology
  • Caffeine / pharmacology
  • Chitinase-3-Like Protein 1
  • Colitis / chemically induced
  • Colitis / complications
  • Colitis / genetics
  • Colitis / metabolism*
  • Colitis / pathology
  • Colitis / prevention & control
  • Colon / drug effects
  • Colon / metabolism*
  • Colon / pathology
  • Colonic Neoplasms / etiology
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / prevention & control
  • DNA Damage
  • Dextran Sulfate
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • HT29 Cells
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Lectins / genetics
  • Lectins / metabolism
  • Male
  • Mice, Inbred BALB C
  • Oxidative Stress / drug effects
  • RNA, Messenger / metabolism
  • Up-Regulation


  • Adipokines
  • Anti-Inflammatory Agents
  • Anticarcinogenic Agents
  • CHI3L1 protein, human
  • Chil1 protein, mouse
  • Chitinase-3-Like Protein 1
  • Glycoproteins
  • Lectins
  • RNA, Messenger
  • Caffeine
  • Dextran Sulfate
  • Hydrogen Peroxide