Cellular localization of cyclo-oxygenase isozymes in Crohn's disease and colorectal cancer

Deregulation of cyclo-oxygenase isozyme expression has been shown to be a c onsistent feature of inflammatory bowel diseases and colorectal cancer in h umans. This study investigated the cellular localization of aberrant cyclo- oxygenase expression in normal and diseased colon. Biopsies of seven normal colonic tissues, eight tissue samples from patients suffering from Crohn's disease, five polyps from patients with familiar adenomatous polyposis col i, and ten sporadic adenocarcinomas were analyzed using isozyme-selective i mmunoprecipitation, western blotting, and immunohistochemistry. Cyclo-oxyge nase-1 expression was demonstrated in normal human colon, Crohn's disease, and colorectal tumors. In normal colon and also in adenomatous polyps, cycl o-oxygenase-1 specific immuno-signals were localized to epithelial cells of the upper part of the crypts and endocrine cells of the lower part. In Cro hn's disease cyclo-oxygenase-1 expression was restricted to cells of the in flammatory infiltrate. While barely detectable in normal colon, cyclo-oxyge nase-2 protein was strongly increased in epithelial cells located in the up permost part of the crypts, in surface epithelial cells, and in mononuclear cells of the lamina propria of Crohn's disease. The constitutive overexpre ssion of cyclo-oxygenase-2 protein observed in the majority of the adenomat ous polyps and all adenocarcinomas was attributed to both epithelial and in terstitial cells in that the latter predominated in adenomas, and epithelia l cells were the prevailing cyclo-oxygenase-2 expressing cell type in adeno carcinomas. In conclusion, both autocrine and paracrine effects of aberrant cyclo-oxygenase-2 expression may contribute to the development of Crohn's disease and colonic tumor development.