Pathogenesis of malignant pleural mesothelioma

Our plain-English summary of Pathogenesis of malignant pleural mesothelioma, by M.C. Jaurand, J. Fleury-Feith (Respirology, 2005).

The study

• Authors: M.C. Jaurand, J. Fleury-Feith
• Journal: Respirology
• Published: 2005;10(1):2-8
• Type of article: Review
• Cited by: 47 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) results from neoplastic transformation of mesothelial cells. Past asbestos exposure represents the major risk factor for MPM, as the link between asbestos fibres and MPM has been largely proved by epidemiological and experimental studies. Asbestos fibres induce DNA and chromosome damage linked to oxidative stress following phagocytosis. Recently, simian virus 40 (SV40) has been implicated in the aetiology of MPM. The origin of human infection has been associated with SV40-contaminated polio vaccines, although to date, no epidemiological data supports this hypothesis. SV40 may act as a coactivator of asbestos in mesothelial oncogenesis. The transforming potency of SV40 results from the activity of two viral proteins, large T and small t antigens. SV40 infection stimulates production of growth factors elsewhere implicated in autocrine growth of mesothelioma cells and inactivates RASSF1, a gene silenced in MPM. Roles for ionising radiation, chemicals or genetic factors have also been suggested from the observation of sporadic MPM cases or animal studies. Genetic alterations in the tumour suppressor genes, P16/CDKN2A and neurofibromatosis 2 (NF2), are found both in human MPM and in asbestos-exposed Nf2-deficient mice. MPM is still of great international concern. Despite a ban on asbestos use in Western countries, the incidence of MPM is increasing, due to the long delay between asbestos exposure and diagnosis. Moreover, asbestos is still used in developing countries. The implication of other risk factors, especially SV40, supports a need for further research into MPM.

In plain English

This article was an invited review, not a new study. The authors summarized published research on how malignant pleural mesothelioma develops and on its suspected causes. They reported that past asbestos exposure is found in approximately 80% of patients with this cancer. They described laboratory studies indicating that reactive oxygen molecules produced when mesothelial cells engulf asbestos fibres are likely responsible for DNA breakage, and stated that long, thin fibres are the most tumour-causing. They reviewed simian virus 40 (SV40) as a possible additional cause, noting that detection of its DNA in patient samples ranged from 0% to 90% across studies and remains debated. They stated that no epidemiological or animal data support a role for ionising radiation, and that no epidemiological data exist on certain chemicals that cause mesothelioma in animals. Describing their own earlier experiment, they reported that mice with only one copy (hemizygous) of the Nf2 gene developed more peritoneal tumours after asbestos exposure than normal mice. The authors concluded that the mesothelium must be considered a potential target of other environmental factors.

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: Invited narrative review of published research. The authors also describe their own earlier mouse experiment.
• Who was studied: No new study population. The review covered published epidemiological, animal and cell-culture research on malignant pleural mesothelioma.
• Exposure: Asbestos fibres: the amphiboles crocidolite, amosite and anthophyllite, and the serpentine chrysotile. Also reviewed: simian virus 40 (SV40), ionising radiation, certain chemicals, a fibre type from the Cappadocia region of Turkey, man-made vitreous fibres, and genetic factors.
• Main results:
  • Among patients presenting with malignant pleural mesothelioma, past asbestos exposure is found in approximately 80%.
  • In laboratory studies, reactive oxygen molecules produced after mesothelial cells engulf asbestos fibres are likely responsible for DNA breakage.
  • Fibre size matters: long, thin fibres are the most tumour-causing.
  • Detection of SV40 DNA in samples from mesothelioma patients ranged from 0% to 90% across studies.
  • Two tumour suppressor genes, P16/CDKN2A and NF2, are frequently mutated in malignant pleural mesothelioma. TP53 shows few mutations.
  • No epidemiological or animal experimental data support a role for ionising radiation in malignant pleural mesothelioma.
  • In the authors' earlier experiment, mice hemizygous for the Nf2 gene had higher rates of tumoural ascites and peritoneal tumours after asbestos exposure than wild-type mice.
  • European and Australian studies predict that deaths from mesothelioma will peak around 2020 to 2030.
• The authors' conclusion: The authors concluded that, because fibres deposited in the lung can reach the pleura, the mesothelium must be considered a potential target of other adverse environmental factors.
• Limitations the authors state:
  • The presence of SV40 in biological samples remains debated, including possible false-positive results from laboratory contamination.
  • Chemicals reported to induce mesothelioma in animals have no epidemiological data on effects in humans.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelial Cells, Asbestos Exposure, Oxidative Stress, Phagocytosis, SV40, Oncogenesis, Mesothelioma.

Related studies

• The pathogenesis of mesothelioma — M. Carbone, R.A. Kratzke, et al. (2002)
• SV40-induced expression of calretinin protects mesothelial cells from asbestos cytotoxicity and may be a key factor contributing to mesothelioma pathogenesis — T. Henzi, W.V. Blum, et al. (2009)
• Animal models of malignant mesothelioma — A.B. Kane (2006)
• The role of SV40 in malignant mesothelioma and other human malignancies — M.A. Pershouse, S. Heivly, et al. (2006)
• Aberrant methylation profile of human malignant mesotheliomas and its relationship to SV40 infection — M. Suzuki, S. Toyooka, et al. (2005)
• SV40 enhances the risk of malignant mesothelioma among people exposed to asbestos: a molecular epidemiologic case-control study — A. Cristaudo, R. Foddis, et al. (2005)

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