Association of enhanced cyclooxygenase-2 expression with possible local immunosuppression in human colorectal carcinomas.
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.
Kojima
M
M
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. kojimam@jwci.org
Morisaki
T
T
Uchiyama
A
A
Doi
F
F
Mibu
R
R
Katano
M
M
Tanaka
M
M
D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy; D007527:Isoenzymes / Q000032:analysis* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis* / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013223:Statistics as Topic; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone