Nitric oxide synthase expression and nitric oxide production in human colon carcinoma tissue

Background and Objectives: Nitric oxide (NO), the production of which is de pendent on NO synthase (NOS), has been shown to contribute to various patho geneses in cancer. The aim of this study was to determine whether inducible NO synthase (iNOS) is overexpressed in human colon carcinoma tissue, and w hether NO is produced in tumor tissue. Methods: We investigated iNOS mRNA expression in 24 human colon carcinoma t issue specimens by reverse transcription-polymerase chain reaction (RT-PCR) . We then examined the expression of iNOS protein and nitrotyrosine, which indicates NO production in tissue, by immunohistochemistry. The possible im munosuppressive role of NO produced by colon carcinoma cells was analyzed i n vitro. Results: Semiquantitative RT-PCR analysis showed that iNOS mRNA expression in carcinoma tissues is elevated significantly compared to that in noncarci noma tissue. Immunohistochemistry revealed that iNOS and nitrotyrosine are expressed strongly in carcinoma tissues. In vitro experiments showed that t he supernatant from a culture of cytokine-treated colon carcinoma cells, wh ich contained high levels of NO, significantly reduced the phytohemagglutin in (PHA)-stimulated, human lymphocyte proliferative response (60% of the co ntrol value). Conclusions: In human colon carcinoma tissue, iNOS mRNA, protein, and NO pr oducts are overexpressed and may contribute to tumor-related immunosuppress ion. J. Surg, Oncol. 1999;70:222-229. (C) 1999 Wiley-Liss, Inc.