Manganese superoxide dismutase in healthy human pleural mesothelium and in malignant pleural mesothelioma

Our plain-English summary of Manganese superoxide dismutase in healthy human pleural mesothelium and in malignant pleural mesothelioma, by K. Kahlos, S. Anttila, T. Asikainen, et al (American Journal of Respiratory Cell and Molecular Biology, 1998).

The study

• Authors: K. Kahlos, S. Anttila, T. Asikainen, K. Kinnula, K.O. Raivio, K. Mattson, K. Linnainmaa, V.L. Kinnula
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1998;18(4):570-80
• Cited by: 58 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

We hypothesized that manganese superoxide dismutase (MnSOD), known to be induced in rat mesothelial cells by asbestos fibers, cytokines, and hyperoxia, may also be induced in asbestos-related pleural diseases such as mesothelioma. MnSOD was assessed in healthy human pleural mesothelium (n = 6), in biopsy samples of human pleural mesothelioma (n = 7), in transformed nonmalignant human mesothelial cells (Met5A), and in two human mesothelioma cell lines (M14K and M38K) established from the tumor tissue of mesothelioma patients. There was no MnSOD immunoreactivity in five of the six samples of healthy pleural mesothelium, whereas MnSOD immunoreactivity was high in the tumor cells in all the mesothelioma samples. Northern blotting, immunohistochemistry, Western blotting, and specific activity measurements showed lower MnSOD in the nonmalignant Met5A mesothelial cells than in the M14K and M38K mesothelioma cells. In additional experiments the mesothelial and mesothelioma cells were exposed to menadione, which generates superoxide intracellularly, and to epirubicin, a cytotoxic drug commonly used to treat mesothelioma. The M38K mesothelioma cells were most resistant to menadione and epirubicin when assessed by LDH release or by adenine nucleotide (ATP, ADP, and AMP) depletion. These same cells showed not only the highest MnSOD levels, but also the highest mRNA levels and activities of catalase, whereas glutathione peroxidase and glutathione reductase levels did not differ significantly. We conclude that MnSOD expression is low in healthy human pleural mesothelium and high in human malignant mesothelioma. The most resistant mesothelioma cells contained coordinated induction of MnSOD and catalase.

In plain English

This Finnish laboratory study measured manganese superoxide dismutase (MnSOD), an enzyme that protects cells from oxidant injury, in the pleura. The authors stained six samples of healthy visceral pleura from people having lung surgery for other reasons, and seven biopsy samples of pleural mesothelioma. The mesothelioma patients were men with occupational asbestos exposure, judged from work histories and lung fiber content. The article does not name fiber types. The authors also compared a nonmalignant mesothelial cell line (Met5A) with two mesothelioma cell lines (M14K and M38K). Five of the six healthy samples showed no MnSOD staining. All seven tumor samples showed moderate or intense staining, with no tendency for higher fiber content to go with stronger staining. Both mesothelioma cell lines had more MnSOD protein than Met5A. M38K had the highest MnSOD and catalase activity, and it was the most resistant to menadione, an oxidant, and to the chemotherapy drug epirubicin. The authors concluded that MnSOD induction may be a typical feature of asbestos-related mesothelioma, but that its clinical implications remain to be investigated.

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 study of human tissue samples (immunohistochemistry) and cultured human cell lines (enzyme, gene-expression and cell-injury experiments)
• Who was studied: Healthy visceral pleura from six people who had lung surgery for reasons other than mesothelioma or pleural disease; seven pleural mesothelioma tissue samples from Finnish patients (clinical data given for eight male patients aged 43 to 72, one of whom had only a cell line available); one SV40-transformed nonmalignant human mesothelial cell line (Met5A) and two mesothelioma cell lines (M14K and M38K)
• Exposure: The mesothelioma patients had occupational asbestos exposure, established from work histories and lung fiber content. No fiber type is named. In the laboratory, the cells were exposed to menadione (an oxidant) and to epirubicin (a chemotherapy drug).
• Main results:
  • Healthy pleura: five of the six samples showed no MnSOD immunoreactivity.
  • Mesothelioma tissue: all seven samples showed moderate or intense MnSOD immunoreactivity in the malignant cells.
  • In the mesothelioma patients, higher lung fiber content did not tend to go with greater MnSOD reactivity.
  • No correlation was found between tumor stage and MnSOD expression.
  • MnSOD staining appeared more intense in mixed-histology tumors than in epithelial tumors.
  • Cell lines: MnSOD protein was significantly higher in both mesothelioma cell lines (M14K and M38K) than in the nonmalignant Met5A cells.
  • Cell lines: MnSOD activity was significantly higher in M38K cells than in M14K or Met5A cells.
  • Menadione exposure: cell energy state was best maintained in M38K cells, intermediate in M14K cells and lowest in Met5A cells.
  • Epirubicin exposure: Met5A cells showed the greatest injury, and M38K cells were completely resistant at the concentration tested.
  • The M38K cell line was the most resistant to both the oxidant and epirubicin. It also had the highest MnSOD activity and the highest catalase activity.
  • Other enzymes: glutathione peroxidase activity showed only a nonsignificant tendency to increase in M38K cells. Glutathione reductase activity was similar in all three cell lines, and CuZnSOD activity did not differ between them.
• The authors' conclusion: The authors concluded that MnSOD induction may be a typical feature of asbestos-related mesothelioma. Whether it matters for diagnosis, or plays a role in the tumor's drug resistance in the body, remains to be investigated.
• Limitations the authors state:
  • Healthy pleural tissue from the mesothelioma patients themselves was not available.
  • Findings in cultured tumor cells may not represent the situation in the body.
  • No sarcomatous mesothelioma samples were available.
  • For the M14K cell line, the original tumor was not available.

Topics

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

Medical terms in this study, explained in our Lexicon: Superoxide, Mesothelium, Pleural Mesothelioma, Mesothelial Cells, Cytokine, Asbestos-Related Pleural Disease, Mesothelioma, Biopsy.

Related studies

• Manganese superoxide dismutase in human pleural mesothelioma cell lines — V.L. Kinnula, P. Pietarinen-Runtti, et al. (1996)
• Induction of manganese superoxide dismutase gene expression in bronchoepithelial cells after rockwool exposure — J. Marks-Konczalik, A. Gillissen, et al. (1998)
• Ultrastructural and chromosomal studies on manganese superoxide dismutase in malignant mesothelioma — V.L. Kinnula, T. Torkkeli, et al. (2004)
• Transfection of a manganese-containing superoxide dismutase gene into hamster tracheal epithelial cells ameliorates asbestos-mediated cytotoxicity — B.T. Mossman, P. Surinrut, et al. (1996)
• Manganese superoxide dismutase genotypes and asbestos-associated pulmonary disorders — A. Hirvonen, J. Tuimala, et al. (2002)
• Polymorphisms of glutathione-S-transferase M1 and manganese superoxide dismutase are associated with the risk of malignant pleural mesothelioma — S. Landi, F. Gemignani, et al. (2007)

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