TITLE

TNF α MODULATION OF E-CADHERIN IN AN EX VIVO MODEL OF BARRETT'S METAPLASIA

AUTHOR(S)
Harper, E.; Harrison, R.; Cooper, B.T.; Jankowski, J.A.Z.; Spychal, R.T.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA90
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Introduction: The majority of oesophageal adenocarcinoma arises from Barrett's metaplasia (BM) following a metaplasia-dysplasiacarcinoma sequence. E-cadherin expression is down regulated along this progression, and TNFα expression is increased. We have demonstrated in an intestinal cell culture model that TNFα stimulation results in down regulation of E-cadherin. We aim to investigate the modulation of E-cadherin by TNFα in an ex-viva tissue culture model. Methods: Specimens of Barrett's metaplasia were obtained endoscopically. Each biopsy was divided, half for histology and half for tissue culture. Matched normal squamous and duodenal epithelium was also taken from each patient. Biopsies were divided and randomly assigned to culture with or without TNFα at 50 ng/ml by standard tissue explant methods. Specimens were then harvested at time points and processed for Western blotting. LDH levels in the culture media were used as a measure of viability, along with morphological assessment and immunohistochemistry (IHC) with Ki-67 antibody. Results: Nine sets of biopsies were cultured. LDH assay, morphology and Ki-67 IHC confirmed viability at 18 hours. By 24 hours media LDH levels had increased and there was evidence of necrosis, with reduced Ki-67 expression indicating a reduction in cell division. E-cadherin protein expression as assessed by Western blotting did not show any evidence of down regulation in response to TNFα when compared to uncultured specimens or those cultured in TNFα free media. This was also true for normal squamous and duodenal mucosa. Conclusion: We demonstrate the short life span of explant tissue samples ex viva. In addition the effects of TNFα on E-cadherin expression are in contrast to our previous work. This may reflect the fact that BM has a TNFα rich microenvironment and that its receptors are already maximally stimulated. It is also possible that ex viva TNFα does not modulate...
ACCESSION #
9747890

 

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