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Association of Enhanced Cyclooxygenase-2 Expression With Possible Local Immunosuppression in Human Colorectal Carcinomas

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Abstract

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.

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Authors and Affiliations

  1. Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Masayuki Kojima MD, Akihiko Uchiyama MD, Fukashi Doi MD, Ryuichi Mibu MD & Masao Tanaka MD

  2. Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Takashi Morisaki MD & Mitsuo Katano MD

  3. Department of Molecular Therapeutics, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA, 90404

    Masayuki Kojima MD

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  1. Masayuki Kojima MD
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  2. Takashi Morisaki MD
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  3. Akihiko Uchiyama MD
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  4. Fukashi Doi MD
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  5. Ryuichi Mibu MD
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Correspondence to Masayuki Kojima MD.

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Kojima, M., Morisaki, T., Uchiyama, A. et al. Association of Enhanced Cyclooxygenase-2 Expression With Possible Local Immunosuppression in Human Colorectal Carcinomas. Ann Surg Oncol 8, 458–465 (2001). https://doi.org/10.1007/s10434-001-0458-x

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  • DOI: https://doi.org/10.1007/s10434-001-0458-x

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