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

Expression of cyclooxygenase 2 (COX-2) is believed to play an important rol e in adenoma formation in murine polyposis models, and inhibition of COX-2 activity may, at least, partly explain the chemopreventative activity of no n-steroidal anti-inflammatory drugs against colorectal cancer in humans. Ho wever, the mechanism by which COX-2 acts in intestinal tumorigenesis remain s unresolved because of conflicting data on the cellular localization of CO X-2 in intestinal mucosa. Using immunohistochemistry with specific COX-2 an tiserum, we have shown that COX-2 protein is localized to interstitial cell s at the base of and within adenomas of the small and large intestine of mu ltiple intestinal neoplasia (Min) mice. No COX-2 staining was observed in d ysplastic epithelial cells within adenomas or in histologically normal epit helium. Moreover, COX-2 staining was observed in lamina propria cells of hi stologically normal intestine of Min mice. No staining was demonstrated in wild-type littermates, The rat monoclonal antibody F4/80 was used to show t hat 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 adenoma s and also on histologically normal epithelium. Up-regulation of COX-2 expr ession in lamina propria macrophages may precede loss of the second functio nal Ape allele in epithelial cells before adenoma formation in the Min mous e model of intestinal tumorigenesis.