Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2016; 22(37): 8334-8348
Published online Oct 7, 2016. doi: 10.3748/wjg.v22.i37.8334
Characterisation of colonic dysplasia-like epithelial atypia in murine colitis
Sarron Randall-Demllo, Ruchira Fernando, Terry Brain, Sukhwinder Singh Sohal, Anthony L Cook, Nuri Guven, Dale Kunde, Kevin Spring, Rajaraman Eri
Sarron Randall-Demllo, Sukhwinder Singh Sohal, Dale Kunde, Rajaraman Eri, School of Health Sciences, University of Tasmania, Launceston, Launceston TAS 7250, Australia
Ruchira Fernando, Terry Brain, Department of Pathology, Launceston General Hospital, Launceston, Launceston TAS 7250, Australia
Anthony L Cook, Wicking Dementia Research and Education Centre, University of Tasmania, Hobart TAS 7005, Australia
Nuri Guven, Division of Pharmacy, School of Medicine, University of Tasmania, Hobart TAS 7005, Australia
Sukhwinder Singh Sohal, Breathe Well Centre of Research Excellence for Chronic Respiratory Disease and Lung Ageing, School of Medicine, University of Tasmania, Hobart TAS 7005, Australia
Kevin Spring, Medical Oncology, Ingham Institute for Applied Medical Research, Liverpool, Liverpool NSW 2170, Australia
Kevin Spring, Liverpool Clinical School, Western Sydney University, Richmond NSW 2753, Australia
Kevin Spring, South West Sydney Clinical School, University of New South Wales, Sydney NSW 2052, Australia
Author contributions: Randall-Demllo S and Eri R conceived and designed the experiments; Randall-Demllo S performed experiments and collected data; Randall-Demllo S, Fernando R and Brain T analysed the data; Fernando R, Brain T, Sohal SS, Cook AL, Guven N, Kunde D and Eri R contributed reagents and materials; Randall-Demllo S, Fernando R, Brain T, Sohal SS, Cook AL, Guven N, Kunde D, Spring K and Eri R contributed to writing the manuscript.
Supported by a Clifford Craig Medical Research Trust project grant and Cancer Council Tasmania (to Kunde D and Eri R); a Bowel Cancer Funding Partners PhD scholarship generously funded by Rotary District 9830, Australian Rotary Health and the University of Tasmania (to Randall-Demllo S).
Institutional review board statement: The study was reviewed and approved by the University of Tasmania Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Tasmania animal Ethics Committee. Ethics Committee Number: A13329.
Conflict-of-interest statement: No conflict of interest exists.
Data sharing statement: All data relevant to this study are included in the paper and its supporting information.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Rajaraman Eri, DVM, PhD, School of Health Sciences, University of Tasmania, Launceston, Churchill Avenue, Launceston TAS 7250, Australia. rderi@utas.edu.au
Telephone: +61-3-62262999
Received: June 27, 2016
Peer-review started: June 28, 2016
First decision: July 29, 2016
Revised: August 15, 2016
Accepted: September 6, 2016
Article in press: September 6, 2016
Published online: October 7, 2016
Processing time: 95 Days and 3.3 Hours
Core Tip

Core tip: Patients with ulcerative colitis (UC) are at increased risk of developing colonic cancer. Understanding progression to early dysplastic change in the UC-associated inflammation in the colon required a suitable animal model. Winnie mice develop a UC-like chronic colitis and endoplasmic reticulum stress due to a Muc2 mutation encoding a misfolded mucin-2. We hypothesised that exacerbation of pre-existing chronic inflammation using colitogenic dextran sulphate sodium in a model of spontaneous colitis would induce colorectal tumourigenesis. This study demonstrated that exacerbation of colitis resulted in epithelial hyperplasia in the distal colon and crypt abnormalities resembling dysplasia. Altered expression of genes known to modify tumour growth, specifically Cav1, Ccl5, Myc and Trp53, in Muc2 mutants may predispose to early neoplastic change in the inflamed colon.