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From the Departments of Surgery and Oncology (MKo, AU, FD, RM, MT), and Cancer Therapy and Research (TM, MKa), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Correspondence: Address correspondence and reprint requests to: Masayuki Kojima, MD, Department of Molecular Therapeutics, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404; Fax: 310-979-5529; E-mail: kojimam{at}jwci.org
Background: Prostaglandin (PG) E2 has an influence on antitumor lymphocyte reactions and causes local immunosuppression at tumor sites. The contribution of cyclooxygenase (COX), a key enzyme in PGE2 synthesis, to this effect is still unclear. We examined if cyclooxygenase (COX)-2 is involved in local immunosuppression in human colon carcinoma cell lines and in clinical tumor specimens.
Methods: PGE2 concentrations were measured in culture media from a highly COX-2-expressing human colon carcinoma cell line (CE-1) and other cell lines. Lymphocyte proliferation in response to a mitogen was used to evaluate immunosuppression in tumor cell-lymphocyte cocultures with and without selective COX-2 inhibitor NS-398. We also evaluated expression of COX-2 mRNA in surgical specimens of colorectal carcinoma by reverse transcription polymerase chain reaction (RT-PCR) and COX-2 protein by immunohistochemistry, correlating COX-2 expression with clinicopathologic features.
Results: CE-1 cells produced large amounts of PGE2, which was significantly inhibited by NS-398. The proliferation index of lymphocytes cocultured with CE-1 cells was significantly less than that of control lymphocytes; again, this effect was inhibited by NS-398. While human colorectal carcinoma tissue expressed more COX-2 mRNA and protein than nonneoplastic tissue, no significant correlation was found between COX-2 levels and clinicopathologic features.
Conclusions: Overexpression of COX-2 in colon cancer may cause local immunosuppression, and COX-2 inhibitors might be therapeutically useful against these tumors.
Key Words: Colorectal carcinoma • COX-2 • PGE2 • Immunosuppression • RT-PCR
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