Alterations in classical cadherins associated with progression in ulcerative and Crohn's colitis

Jankowski, J A, Bedford, F K, Boulton, R A, Cruickshank, N, Hall, C, Elder, J, Allan, R, Forbes, A, Kim, Y S, Wright, N A and Sanders, D S (1998) Alterations in classical cadherins associated with progression in ulcerative and Crohn's colitis. Laboratory Investigation, 78 (9). pp. 1155-67. ISSN 0023-6837

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Abstract

Human colitis is a condition associated with a spectrum of altered morphologic changes and cellular adhesion. The role of cadherins, which are powerful morphoregulatory cell adhesion molecules, in colitis is provocative and as yet unknown. Herein, we present results that suggest a strong correlation between the deregulation of two cadherin molecules, E- and P-cadherins, and the progression of human colitis. We examined the expression and structural integrity of E- and P-cadherins in inflamed, dysplastic, or neoplastic human ulcerative colitis (UC) (n=58), human Crohn's colitis (n = 30), and normal tissue (n = 20) to assess cadherin function in normal and abnormal epithelium. E-cadherin is strongly expressed in normal colorectal epithelium, whereas in left-sided UC it is either down-regulated or has a single-base pair mutation in exon 4 resulting in an amino acid alteration (6 of 58 UC cases). By contrast, P-cadherin is dramatically up-regulated in both Crohn's disease and ulcerative colitis and especially in dysplastic ulcerative tissue. In vitro transfected SW-480 colorectal cells containing E-cadherin mutations identical to those in vivo were associated with increased spontaneous disaggregation compared with cells transfected with wild-type E-cadherin. Based on this evidence, we hypothesize that a small subset of colorectal cells expressing mutant E-cadherin are associated with widespread ulceration, whereas those expressing P-cadherin are associated with a rapidly dividing immature phenotype that includes dysplasia. The differential expression of mutated and wild-type cadherins examined herein are associated with a broad spectrum of abnormal epithelial phenotypes, lymphocyte integrin binding, and resistance to denudation, as is seen in the colitis adenocarcinoma sequence.

Item Type: Article
Uncontrolled Keywords: adult,aged,cadherins,colitis, ulcerative,crohn disease,dna mutational analysis,disease progression,humans,middle aged,nucleotides,reference values,tumor cells, cultured
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
University of East Anglia > Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
University of East Anglia > Faculty of Medicine and Health Sciences > Research Groups > Nutrition
Depositing User: Pure Connector
Date Deposited: 06 Aug 2014 11:48
Last Modified: 25 Jul 2018 09:53
URI: https://ueaeprints.uea.ac.uk/id/eprint/49560
DOI:

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