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

Our plain-English summary of Expression of inducible nitric oxide synthase in healthy pleura and in malignant mesothelioma, by Y. Soini, K. Kahlos, A. Puhakka, et al (British Journal of Cancer, 2000).

The study

• Authors: Y. Soini, K. Kahlos, A. Puhakka, E. Lakari, M. Säily, P. Pääkkö, V. Kinnula
• Journal: British Journal of Cancer
• Published: 2000;83(7):880-6
• Cited by: 40 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

Copyright 2000 Cancer Research Campaign.

In plain English

This laboratory study from Oulu University Hospital, Finland, examined an enzyme called inducible nitric oxide synthase (iNOS) in pleural tissue. The authors stained archived samples from 1976 to 1997: 38 malignant mesotheliomas, 25 cancers that had spread to the pleura from elsewhere (metastatic adenocarcinomas), four samples of inflamed pleura and five of healthy pleura. They also tested four mesothelioma cell lines and one non-malignant mesothelial cell line. The article does not report the patients' asbestos exposure. In four of the five healthy pleura samples the lining cells showed no staining. All four inflamed samples were positive. iNOS was found in 28/38 (74%) mesotheliomas and 24/25 (96%) metastatic adenocarcinomas, and mesotheliomas were significantly more often negative. Sarcomatoid mesotheliomas were more often unstained than epithelial or mixed ones. In mesotheliomas, iNOS was not significantly associated with programmed cell death (apoptosis), blood-vessel density or survival. All five cell lines made iNOS. The authors concluded that nitric oxide production may modulate tumour growth and progression. They also wrote that factors other than asbestos fibres probably cause iNOS induction in mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory pathology study: immunohistochemical staining of archived human tissue samples, plus experiments on cultured cell lines (RT-PCR and immunostaining)
• Who was studied: Archived tissue from the Department of Pathology, Oulu University Hospital, Finland, 1976 to 1997: 38 malignant mesotheliomas (5 women, 33 men, mean age 62.2 years), 25 pleural metastatic adenocarcinomas, 4 cases of inflamed mesothelium and 5 cases of non-neoplastic, non-inflamed pleura. Also four mesothelioma cell lines (M14K, M25K, M28K, M38K) and one non-malignant transformed mesothelial cell line (Met5A).
• Exposure: Not reported. The article gives no information on the patients' asbestos exposure. The factor measured was iNOS expression in the tissue and cells.
• Main results:
  • Healthy pleura: the mesothelial cells in four of five non-neoplastic, non-inflamed samples showed no iNOS staining. In the fifth, a few scattered cells were positive.
  • Inflamed (reactive) mesothelium: all four cases were iNOS positive, with strong expression in one.
  • iNOS positivity was found in 28/38 (74%) of malignant pleural mesotheliomas and 24/25 (96%) of metastatic pleural adenocarcinomas.
  • Mesotheliomas were significantly more often iNOS negative than metastatic adenocarcinomas (P = 0.021 with the polyclonal antibody, P < 0.001 with the monoclonal antibody).
  • Sarcomatoid mesotheliomas showed no staining significantly more often than epithelial or mixed mesotheliomas (P = 0.001 with the polyclonal antibody, P = 0.023 with the monoclonal antibody).
  • In mesotheliomas, iNOS expression was not significantly associated with apoptosis (P = 0.07 monoclonal, P = 0.95 polyclonal) or with vascular density (P = 0.29 monoclonal, P = 0.25 polyclonal). The average apoptotic index was 1.07% and the average number of vessels per high power field was 8.7.
  • In mesotheliomas, no association was found between iNOS staining and patient survival.
  • iNOS mRNA was found in all five cell lines: the four mesothelioma lines and the Met5A mesothelial line.
  • Because pleural metastatic adenocarcinomas showed at least the same iNOS intensity as mesotheliomas, the authors inferred that factors other than asbestos fibres probably cause iNOS induction in mesothelioma.
• The authors' conclusion: The authors concluded that iNOS is prominently expressed in malignant mesothelioma and metastatic pleural adenocarcinoma compared with healthy pleural mesothelium. They wrote that this suggests nitric oxide synthesis modulates the growth and progression of these tumours.
• Limitations the authors state:
  • Some cases could not be stained with the monoclonal antibody because the tissue blocks had run out.
  • The authors noted that the lack of association with vascular density is hard to interpret, because blood-vessel growth is complex and is influenced by iNOS-producing stromal cells in the tumours.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Inducible Nitric Oxide Synthase (iNOS), Pleura, Malignant Mesothelioma, Mesothelioma, Adenocarcinoma, Apoptosis, Immunohistochemistry, Mesothelial Cells.

Related studies

• Endothelial nitric oxide synthase is strongly expressed in malignant mesothelioma but does not associate with vascular density or the expression of VEGF, FLK1 or FLT1 — Y. Soini, A. Puhakka, et al. (2001)
• Early inflammatory response to asbestos exposure in rat and hamster lungs: role of inducible nitric oxide synthase — M. Dörger, A.M. Allmeling, et al. (2002)
• Dual role of inducible nitric oxide synthase in acute asbestos-induced lung injury — M. Dörger, A.M. Allmeling, et al. (2002)
• Regulation of nitric oxide synthase induction by iron and glutathione in asbestos-treated human lung epithelial cells — S.H. Park, A.E. Aust (1998)
• Simian virus 40 infection down-regulates the expression of nitric oxide synthase in human mesothelial cells — E. Aldieri, S. Orecchia, et al. (2004)
• Inducible nitric oxide synthase genetic polymorphism and risk of asbestosis — A. Franko, M. Dodič-Fikfak, et al. (2011)

Browse more research in British Journal of Cancer, or return to medical research.