Cyclooxigenase-2 is upregulated and localized to macrophages in the intestine of min mice

Research output: Contribution to journalArticle

Authors

  • MA Hull
  • J K Booth
  • A Tisbury
  • N Scott
  • P Clissold
  • AF Markham
  • PL Coletta

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)1399-1405
JournalBritish Journal of Cancer
Volume79
Issue number9/10
Publication statusPublished - Mar 1999

Keywords

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