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

Background and Objectives: Nitric oxide (NO), the production of which is dependent on NO synthase (NOS), has been shown to contribute to various pathogeneses in cancer. The aim of this study was to determine whether inducible NO synthase (iNOS) is overexpressed in human colon carcinoma tissue, and whether NO is produced in tumor tissue. Methods: We investigated iNOS mRNA expression in 24 human colon carcinoma tissue 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 immunosuppressive role of NO produced by colon carcinoma cells was analyzed in vitro. Results: Semiquantitative RT-PCR analysis showed that iNOS mRNA expression in carcinoma tissues is elevated significantly compared to that in noncarcinoma tissue. Immunohistochemistry revealed that iNOS and nitrotyrosine are expressed strongly in carcinoma tissues. In vitro experiments showed that the supernatant from a culture of cytokine-treated colon carcinoma cells, which contained high levels of NO, significantly reduced the phytohemagglutinin (PHA)-stimulated, human lymphocyte proliferative response (60% of the control value). Conclusions: In human colon carcinoma tissue, iNOS mRNA, protein, and NO products are overexpressed and may contribute to tumor-related immunosuppression. J. Surg, Oncol. 1999;70:222-229. (C) 1999 Wiley-Liss, Inc.