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Carcinogenesis Advance Access published online on May 5, 2005
Carcinogenesis, doi:10.1093/carcin/bgi114
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oupjournals.org
Received March 10, 2005
Revised April 23, 2005
Accepted April 26, 2005

CARCINOGENESIS

Effect of inflammation on cyclooxygenase (COX)-2 expression in benign and malignant oesophageal cells

Salem I. Abdalla 1, Ian R. Sanderson 2, and Rebecca C. Fitzgerald 3*

1 Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge, CB2 2XZ, UK; Institute of Cell and Molecular Science, Adult and Paediatric Gastroenterology Department, Barts and the London School of Medicine and Dentistry, London, UK
2 Institute of Cell and Molecular Science, Adult and Paediatric Gastroenterology Department, Barts and the London School of Medicine and Dentistry, London, UK
3 Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge, CB2 2XZ, UK

* To whom correspondence should be addressed.
Rebecca C. Fitzgerald, E-mail: rcf{at}hutchison-mrc.cam.ac.uk


  Abstract

Background: Chronic inflammation has been linked to carcinogenesis in various tissue sites. Barrett's oesophageal epithelium (BE) is a pre-malignant condition in which COX-2 levels are increased. However, it is not clear whether the primary stimulus for the high COX-2 levels is related to inflammation or malignancy. Methods: The effect of exogenous cytokines (IL-1{beta}, IL-10 and IL-13) on COX-2 expression was assessed by western blotting in 3 BE cancer cell lines (SEG-1, BIC-1 and OE33) and a squamous cancer cell line (OE21). Primary tissue was assessed from 17 patients with long BE segments, 13 oesophagitis, 30 oesophageal adenocarcinoma (AC) and 40 normal oesophageal (NE) and duodenal (DU) controls. COX-2 protein expression was determined by western blotting and its tissue localisation was examined using immunohistochemistry. COX-2 protein and the neutrophil marker myeloperoxidase (MPO) were quantified along BE segments. The leukocyte marker CD45 was used to identify any correlation between COX-2 expression and leukocyte cell distribution in AC. Results: IL-1{beta} induced COX-2 expression in SEG-1 cells (p<0.05), whereas IL-10 and IL-13 had no effect. COX-2 protein levels were found to be increased in distal BE>proximal BE>oesophagitis>NE (p<0.001). COX-2 expression in AC was heterogeneous and the overall levels were not significantly increased. The increased COX-2 expression in distal BE was not associated with inflammation (MPO expression). In addition, there was no correlation between COX-2 and CD45 in AC. Conclusion: COX-2 protein expression in the oesophagus appears to be independent of the degree of inflammation.

Keywords: oesophageal adenocarcinoma; prostaglandins; cytokines.
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