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

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.

• Authors: M Kojima, T Morisaki, A Uchiyama, F Doi, R Mibu, M Katano, M Tanaka
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 8 Issue 5 Pg. 458-65 (Jun 2001) ISSN: 1068-9265 [Print] United States
• PMID: 11407522 (Publication Type: Journal Article)

Chemical References

• Isoenzymes
• Membrane Proteins
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases
• Dinoprostone

Topics

• Adenocarcinoma (immunology, pathology)
• Adult
• Aged
• Aged, 80 and over
• Analysis of Variance
• Colorectal Neoplasms (immunology, pathology)
• Cyclooxygenase 2
• Dinoprostone (immunology)
• Female
• Humans
• Immunohistochemistry
• Immunosuppression Therapy
• Isoenzymes (analysis, immunology)
• Lymphocyte Activation (immunology)
• Male
• Membrane Proteins
• Middle Aged
• Prostaglandin-Endoperoxide Synthases (analysis, immunology)
• Reverse Transcriptase Polymerase Chain Reaction
• Statistics as Topic
• Tumor Cells, Cultured