Association of enhanced cyclooxygenase-2 expression with possible local immunosuppression in human colorectal carcinomas

Background: Prostaglandin (PG) E, has an influence on antitumor lymphocyte reactions and causes local immunosuppression at tumor sites. The contributi on of cyclooxygenase (COX), a key enzyme in PGE, synthesis, to this effect is still unclear. We examined if cyclooxygenase (COX)-2 is involved in loca l immunosuppression in human colon carcinoma cell lines and in clinical tum or specimens. Methods: PGE, concentrations were measured in culture media from a highly C OX-2-expressing human colon carcinoma cell line (CE-1) and other cell lines . Lymphocyte proliferation in response to a mitogen was used to evaluate im munosuppression in tumor cell-lymphocyte cocultures with and without select ive COX-2 inhibitor NS-398. We also evaluated expression of COX-2 mRNA in s urgical specimens of colorectal carcinoma by reverse transcription polymera se chain reaction (RT-PCR) and COX-2 protein by immunohistochemistry, corre lating COX-2 expression with clinicopathologic features. Results: CE-1 cells produced large amounts of PGE(2), which was significant ly inhibited by NS-398. The proliferation index of lymphocytes cocultured w ith CE-1 cells was significantly less than that of control lymphocytes; aga in, this effect was inhibited by NS-398. While human colorectal carcinoma t issue expressed more COX-2 mRNA and protein than nonneoplastic tissue, no s ignificant correlation was found between COX-2 levels and clinicopathologic features. Conclusions: Overexpression of COX-2 in colon cancer may cause local immuno suppressisn, and COX-2 inhibitors might be therapeutically useful against t hese tumors.