Manganese superoxide dismutase in human pleural mesothelioma cell lines

Our plain-English summary of Manganese superoxide dismutase in human pleural mesothelioma cell lines, by V.L. Kinnula, P. Pietarinen-Runtti, K. Raivio, et al (Free Radical Biology & Medicine, 1996).

The study

• Authors: V.L. Kinnula, P. Pietarinen-Runtti, K. Raivio, K. Kahlos, K. Pelin, K. Mattson, K. Linnainmaa
• Journal: Free Radical Biology & Medicine
• Published: 1996;21(4):527-32
• Cited by: 41 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Mesothelioma is a malignant pleural or intraperitoneal tumor attributable to asbestos exposure in more than 80% of the cases. Manganese superoxide dismutase (MnSOD), a mitochondrial superoxide radical scavenging enzyme, is low in most tumors but is known to be induced by asbestos fibers and certain cytokines. Induction of MnSOD may be associated in asbestos-related pulmonary diseases in vivo. We investigated here MnSOD specific activity and MnSOD mRNA level using healthy human lung tissue, SV40-transformed human pleural mesothelial cells (Met5A), and six human malignant mesothelioma cell line cells. Total SOD (CuZnSOD + MnSOD) and MnSOD activities were 20.0 +/- 4.8 U/mg protein and 3.2 +/- 1.2 U/mg protein in healthy human lung tissue, and 25.6 +/- 10.7 U/mg and 3.8 +/- 1.0 U/mg in Met5A cells, respectively. In four mesothelioma cell lines MnSOD activity was significantly elevated, the highest activity (30.1 +/- 8.2 U/mg) was almost 10-fold compared to the activity in Met5A cells. The steady state mRNA level of MnSOD was low in Met5A cells and markedly higher in all mesothelioma cell lines roughly in proportion with enzyme activities. Cytotoxicity experiments, which were conducted in four cell lines, indicated that cells containing high MnSOD mRNA level and activity were resistant to the mitochondrial superoxide-producing agent menadione. In conclusion, our results suggest that human mesothelioma may express high levels of MnSOD, which is associated with high oxidant resistance of these cells.

In plain English

This laboratory study from Finland measured an antioxidant enzyme, manganese superoxide dismutase (MnSOD), in six cell lines grown from the tumours or pleural fluid of mesothelioma patients. It compared them with immortalized (SV40-transformed) human pleural mesothelial cells called Met5A and with healthy lung tissue removed during surgery. The cells were not exposed to asbestos in this study. MnSOD activity was higher in four of the six mesothelioma lines (18 to 30 units per milligram protein) than in Met5A cells (3.8) or lung tissue (3.2). The highest was line M38K, at 30.1, almost 10 times the Met5A level. MnSOD messenger RNA was markedly raised in the same four lines. Differences between the lines did not correlate with the fibre content of the patients' lung tissue. When treated with menadione, a chemical that produces oxidants, cells high in MnSOD resisted injury better than cells low in it, and M38K resisted best. The authors concluded that mesothelioma cells may carry high MnSOD levels linked to oxidant resistance. They noted that normal mesothelial cells were difficult to obtain.

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 (in vitro) study of human cell lines and lung tissue, published as a brief communication
• Who was studied: Six malignant mesothelioma cell lines established from the authors' patients in Finland: M9K, M10K, M28K, M33K and M38K from tumour tissue, and M14 from pleural fluid. Comparators were SV40-transformed human pleural mesothelial cells (Met5A) and healthy lung tissue (n = 4) taken from tissue margins during lung tumour surgery.
• Exposure: No asbestos exposure was applied in the experiments. The patients' lung fibre content per gram dry weight was recorded, but fibre type was not specified. The experimental exposure was the oxidant-generating compound menadione at 20 micromolar for 4 hours.
• Main results:
  • Total SOD activity was significantly higher in four of the six mesothelioma cell lines (M10K, M28K, M33K, M38K; range 58-73 U/mg protein) than in Met5A cells (25.6 plus or minus 10.7 U/mg protein) or healthy lung (20.0 plus or minus 4.8 U/mg protein, n = 4).
  • MnSOD activity was higher in the same four mesothelioma cell lines (range 18-30 U/mg) than in Met5A cells (3.8 plus or minus 1.0 U/mg) or lung tissue (3.2 plus or minus 1.2 U/mg).
  • The highest MnSOD activity was in M38K cells (30.1 plus or minus 8.2 U/mg), almost 10 times that of Met5A cells.
  • Variation in MnSOD activity between the mesothelioma cell lines did not correlate with the fibre content of the patients' lung tissue.
  • Both 1 kb and 4 kb MnSOD mRNA species were markedly elevated in four mesothelioma cell lines (M10K, M28K, M33K, M38K). mRNA expression was highest in M38K.
  • Of four cell lines exposed to menadione (high MnSOD: M38K, M28K; low MnSOD: Met5A, M9K), oxidant sensitivity correlated with MnSOD activity. M38K cells were the most resistant, judged by maintenance of cellular adenine nucleotides.
• The authors' conclusion: The authors concluded that MnSOD activity was increased in four of six mesothelioma cell lines compared with transformed pleural mesothelial cells and healthy lung. They also concluded that the high-MnSOD mesothelioma cells were far more resistant to oxidant exposure in vitro. They suggested that the high resistance of mesothelioma to cytotoxic drugs may also be partly related to high MnSOD activity.
• Limitations the authors state:
  • Normal human mesothelial cells were not studied in situ because they are difficult to obtain. The comparison cells (Met5A) were SV40-transformed, immortal but nontumorigenic.
  • Lung tissue, used as an additional comparison, contains many cell types, some known to have high antioxidant enzyme levels.
  • MnSOD induction in the mesothelioma cell lines could be related to the cell culture itself, not only to fibre burden or histological subtype.

Topics

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

Medical terms in this study, explained in our Lexicon: Superoxide, Pleural Mesothelioma, Mesothelioma, Asbestos Exposure, Cytokine, SV40, Mesothelial Cells, Malignant Mesothelioma.

Related studies

• Manganese superoxide dismutase in healthy human pleural mesothelium and in malignant pleural mesothelioma — K. Kahlos, S. Anttila, et al. (1998)
• Induction of manganese superoxide dismutase gene expression in bronchoepithelial cells after rockwool exposure — J. Marks-Konczalik, A. Gillissen, et al. (1998)
• 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)
• Ultrastructural and chromosomal studies on manganese superoxide dismutase in malignant mesothelioma — V.L. Kinnula, T. Torkkeli, et al. (2004)
• 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)

Browse more research in Free Radical Biology & Medicine, or return to medical research.