Expression of inducible nitric oxide synthase in healthy pleura and in malignant mesothelioma

• Published in: British journal of cancer 2000-10, Vol.83 (7), p.880-886
• Main Authors: Soini, Y, Kahlos, K, Puhakka, A, Lakari, E, Säily, M, Pääkkö, P, Kinnula, V
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - blood supply; Adenocarcinoma - enzymology; Adenocarcinoma - secondary; Antibodies; Apoptosis; Apoptosis - physiology; Asbestos; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Cell Line, Transformed; DNA damage; Drug Resistance; Epidemiology; Epithelium - enzymology; Factor VIII - immunology; Female; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Male; Medical sciences; Mesothelioma; Mesothelioma - blood supply; Mesothelioma - enzymology; Mesothelioma - pathology; Metastasis; Middle Aged; Molecular Medicine; Nitric oxide; Nitric Oxide Synthase - biosynthesis; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase - immunology; Nitric Oxide Synthase Type II; Nitrogen; Oncology; Pathogenesis; Pleura - enzymology; Pleural Neoplasms - blood supply; Pleural Neoplasms - enzymology; Pleural Neoplasms - secondary; Pleurisy - enzymology; Pneumology; Regular; regular-article; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Tumor Cells, Cultured; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1054/bjoc.2000.1384

In this study we investigated the immunohistochemical expression of inducible nitric oxide synthase (iNOS) in a set of normal pleural mesothelial tissues, malignant mesotheliomas, mesothelioma cell lines and metastatic pleural adenocarcinomas. Furthermore, the expression of mRNA was assessed in four malignant mesothelioma cell lines in culture. Apoptosis and vascular density in malignant mesotheliomas was assessed by the TUNEL method and by immunohistochemistry with an antibody against FVIII-related antigen. Immunohistochemically mesothelial cells in non-neoplastic healthy pleural tissues were mostly negative for iNOS. Positivity for iNOS was observed in 28/38 (74%) and 24/25 (96%) of malignant mesotheliomas and metastatic pleural adenocarcinomas, respectively. Epithelial and mixed mesotheliomas expressed more often strong iNOS immunoreactivity compared to the sarcomatoid subtype ( P = 0.023). Moreover, metastatic adenocarcinomas expressed more often iNOS positivity than mesotheliomas ( P = 0.021). Experiments with the cell lines confirmed that malignant mesothelioma cells are capable of synthesizing iNOS. No significant association was found between iNOS expression and apoptosis or vascular density in malignant mesotheliomas. The higher expression of iNOS in the epithelial subtype of mesothelioma and pleural metastatic adenocarcinoma might be due to an increased sensitivity of these cell types to cytokine-mediated iNOS upregulation. The strong expression of iNOS suggests a putative role for NO in the growth and progression of these tumours. © 2000 Cancer Research Campaign