Cyclooxygenase 2 expression is increased in the stroma of colon carcinomasfrom IL-10(-/-) mice

Background & Aims: The pathological and molecular changes associated with c olitis-associated colorectal cancer and sporadic colorectal cancer are cons idered to be distinct. Therefore, we have used a mouse model of ulcerative colitis to determine if expression of the enzyme cyclooxygenase (COX)-2 is increased in colitis-associated tumors. Methods: Reverse-transcription poly merase chain reaction and Western analysis were used to determine if COX-2 expression is increased in these tumors; in situ hybridization and immunohi stochemistry were used to determine the localization of COX-2. Results: Inc reased levels of COX-2 messenger RNA and protein were detected in interleuk in (IL)-10 (-/-) tumors and in an inflamed region of the colon that contain ed no macroscopically detected tumors. This expression was localized to the inflammatory cells associated with ulcerated regions of the tumor by in si tu hybridization and immunohistochemistry. Increased COX-2 expression was a lso associated with the areas of the tumor expressing cu-smooth muscle acti n, which is a molecular marker for subepithelial myofibroblasts. The associ ation between COX-2 expression and subepithelial myofibroblasts was also no ted in tumors derived from the multiple intestinal neoplasia mice (Min/+) a nd from carcinogen-induced tumors. Conclusions: These results indicate that COX-2 is expressed very early in the pathogenesis of colitis-associated tu mors, and that the expression pattern is similar to that seen in tumors fro m azoxymethane-treated and Min/+ mice.