title: 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.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. kojimam@jwci.org
authors.forename: M
authors.initials: M
authors.lastname: Kojima
authors.forename: T
authors.initials: T
authors.lastname: Morisaki
authors.forename: A
authors.initials: A
authors.lastname: Uchiyama
authors.forename: F
authors.initials: F
authors.lastname: Doi
authors.forename: R
authors.initials: R
authors.lastname: Mibu
authors.forename: M
authors.initials: M
authors.lastname: Katano
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
mesh_terms: 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
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone