Cobby, E.; Bryan, R.; Campbell, M.; Harrison, R.; Jankowski, J.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA38
Academic Journal
Introduction: Barrett's metaplasia is a known premalignant lesion associated with a chronic inflammatory cell infiltrate. Recently work from our and other groups have identified some of the important inflammatory cytokines expressed, but their association along the metaplasia-dysplasia-adenocarcinoma sequence has not been fully elucidated. In particular it has been shown that the pro-inflammatory cytokine tumour necrosis factor alpha (TNFα) may downregulate E-cadherin (the prime epithelial cell-cell adhesion molecule) expression with consequential effects on differentiation and migration. However, ulceration in established Barrett's metaplasia is very rare and it has been postulated that upregulation of other cell-cell adhesion molecules may occur to prevent Joss of tissue integrity. Aim: To assess the co-expression of cytokines and P-cadherin (the cadherin most associated with proliferating and migrating cells) along the metaplasia-dysplasia-adenocarcinoma sequence. Methods and Results: We assessed expression of P-cadherin and interferon gamma (IFNγ) by routine immunocytochemistry and Western blotting on 10 patients from each of the following tissue types: normal oesophagus; reflux oesophagitis; Barrett's metaplasia; Barrett's dysplasia; oesophageal adenocarcinoma; lymph node adenocarcinoma. P-cadherin expression was upregulated along the metaplasia-dysplasia-adenocarcinoma sequence being expressed in predominantly proliferating cells. Similarly IFNγ was upregulated in the same tissues and was significantly correlated with P-cadherin expression. IFNγ was expressed in both the inflammatory and epithelial cells. Conclusions: This data lends further support to the notion that cytokines may regulate cadherin expression in the remodelling of epithea cells arising in the background of chronic mucosal inflammation. In addition this correlation is currently being tested in functional assays in order to assess the mechanism of cytokine...


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