Regular Article

British Journal of Cancer (1999) 79, 1399–1405. doi:10.1038/sj.bjc.6690224 www.bjcancer.com
Published online 26 February 1999

Cyclooxygenase 2 is up-regulated and localized to macrophages in the intestine of Min mice

M A Hull1, J K Booth2, A Tisbury1, N Scott2, C Bonifer1, A F Markham1 and P L Coletta1

  1. 1Molecular Medicine Unit, University of Leeds, Leeds, UK
  2. 2Department of Histopathology, St James's University HospitalS, Leeds LS9 7TF, UK

Correspondence: MA Hull, Division of Medicine, Clinical Sciences Building, St James's University Hospital, Leeds LS9 7TF, UK

Received 27 May 1998; Revised 28 July 1998; Accepted 29 July 1998.

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Abstract

Expression of cyclooxygenase 2 (COX-2) is believed to play an important role in adenoma formation in murine polyposis models, and inhibition of COX-2 activity may, at least, partly explain the chemopreventative activity of non-steroidal anti-inflammatory drugs against colorectal cancer in humans. However, the mechanism by which COX-2 acts in intestinal tumorigenesis remains unresolved because of conflicting data on the cellular localization of COX-2 in intestinal mucosa. Using immunohistochemistry with specific COX-2 antiserum, we have shown that COX-2 protein is localized to interstitial cells at the base of and within adenomas of the small and large intestine of multiple intestinal neoplasia (Min) mice. No COX-2 staining was observed in dysplastic epithelial cells within adenomas or in histologically normal epithelium. Moreover, COX-2 staining was observed in lamina propria cells of histologically normal intestine of Min mice. No staining was demonstrated in wild-type littermates. The rat monoclonal antibody F4/80 was used to show that COX-2-positive cells represented a subset of the macrophage population present in the intestine of Min mice. Localization of COX-2 to macrophages implies a paracrine effect of COX-2 function on epithelial cells in adenomas and also on histologically normal epithelium. Up-regulation of COX-2 expression in lamina propria macrophages may precede loss of the second functional Apc allele in epithelial cells before adenoma formation in the Min mouse model of intestinal tumorigenesis.

Keywords:

adenoma, cyclooxygenase, immunohistochemistry, macrophage, Min mouse, prostaglandin

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