Fluoro-edenite induces fibulin-3 overexpression in non-malignant human mesothelial cells

Our plain-English summary of Fluoro-edenite induces fibulin-3 overexpression in non-malignant human mesothelial cells, by V. Rapisarda, R. Salemi, A. Marconi, et al (Oncology Letters, 2016).

The study

• Authors: V. Rapisarda, R. Salemi, A. Marconi, C. Loreto, A.C. Graziano, V. Cardile, M.S. Basile, S. Candido, L. Falzone, D.A. Spandidos, C. Fenga, M. Libra
• Journal: Oncology Letters
• Published: 2016;12(5):3363-3367
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Exposure to asbestos is associated with the development of mesothelioma. In addition to asbestos, other fibers have been identified as risk factors for malignant and non-malignant diseases of the lungs. Among these, fluoro-edenite (FE) was found in patients from Biancavilla (Sicily, Italy) with pleural and lung disease, suggesting its role for tumor expansion. In this context, the identification of early biomarkers useful for the diagnosis of cancer is mandatory. Fibulin-3 represents an important marker for the diagnosis of mesothelioma. However, it remains to be determined whether it is directly associated with exposure to asbestos-like fibers. In the present study, peripheral blood levels of fibulin-3 from 40 asbestos-exposed workers were compared with those detected in 27 street cleaners from Biancavilla. Intriguingly, the results showed that fibulin-3 levels were higher in the group of street cleaners compared with those of the asbestos-exposed workers, suggesting that these workers used the personal protective equipment according to the current regulations. These data suggest that subjects exposed to FE should be monitored for the risk of mesothelioma. FE and volcanic particulates are probably contained within dust inhaled by street cleaners from Biancavilla during their work activities. Based on these criteria, in this study, such fibers were used to treat mesothelial cells (MeT5A) in order to verify whether fibulin-3 levels are affected by these treatments. The results showed that only treatment with FE was associated with fibulin-3 overexpression at both the transcript and protein levels. It was previously demonstrated that mesothelial cells exhibited low levels of p27 following treatment with FE. Notably, p27 downregulation is associated with stathmin upregulation in cancer, conferring an aggressive phenotype of tumor cells. This observation prompted us to perform a computational evaluation demonstrating the activation of stathmin in lung cancer in patients exposed to asbestos. Overall, it can be speculated that both fibulin-3 and stathmin overexpression may be associated with the malignant transformation of mesothelial cells following exposure to asbestos-like fibers.

In plain English

This Italian study had three parts: blood tests in workers, experiments on cultured cells, and an analysis of a public gene-expression dataset. First, the authors measured blood (plasma) fibulin-3 in 40 male asbestos-exposed workers, mostly removal and disposal workers, and 10 healthy controls. They compared these with 27 Biancavilla street cleaners from an earlier study, described as at high risk of fluoro-edenite exposure. Median levels were 1.51 ng/ml in removal/disposal workers and 1.73 ng/ml in coating workers. These were similar to controls and significantly lower than in the street cleaners. The authors suggested the asbestos workers had used protective equipment properly. Second, non-cancerous human mesothelial cells exposed to fluoro-edenite for 72 hours made significantly more fibulin-3 protein at 50 and 100 µg/ml, with no significant change at 10 µg/ml. They made more fibulin-3 RNA at all three doses. Four volcanic particulates produced no statistically significant increase. Third, the dataset showed significantly higher stathmin RNA levels in lung cancers from 26 asbestos-exposed patients than from 30 unexposed patients. The authors speculated that both changes may be involved in malignant transformation of mesothelial cells after exposure to asbestos-like fibers.

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: Mixed-design study: a comparison of blood fibulin-3 levels in asbestos-exposed workers with earlier data on street cleaners, cell-culture experiments, and a computer analysis of a public gene-expression dataset
• Who was studied: 40 male asbestos-exposed workers (30 removal and disposal workers, 10 coating workers in old pipeline maintenance; mean age 52; 30 of 40 smokers) and 10 healthy male controls, recruited at the Occupational Medicine Unit, University of Catania, Italy. They were compared with 27 street cleaners from Biancavilla from the authors' previous study. The authors described these street cleaners as at high risk of fluoro-edenite exposure. The cell experiments used a non-malignant human pleural mesothelial cell line (Met-5A). The computer analysis used a public dataset of 26 lung cancer samples with confirmed asbestos exposure and 30 non-exposed samples.
• Exposure: Workers: occupational asbestos exposure (fiber type not specified), mean duration 14 years. Cells: fluoro-edenite fibers collected in Biancavilla, and volcanic particulates from Mount Etna (A basalt residues, B volcanic ash, C mixed basalt and cement, D cement), each at 10, 50 and 100 µg/ml for 72 hours.
• Main results:
  • Median plasma fibulin-3 was 1.51 ng/ml (range 0.46 to 3.978) in removal/disposal workers and 1.73 ng/ml (1.012 to 3.59) in coating workers. The authors reported these were similar to the healthy controls.
  • Plasma fibulin-3 was significantly lower in the asbestos-exposed workers than previously observed in the Biancavilla street cleaners.
  • The authors interpreted the lower levels in asbestos workers as suggesting these workers used personal protective equipment according to current regulations.
  • In the asbestos workers, fibulin-3 levels were not associated with duration of asbestos exposure or radiographic score.
  • None of the asbestos workers reported a diagnosis of mesothelioma, asbestosis or pleural plaques.
  • Mesothelial cells exposed to fluoro-edenite at 50 and 100 µg/ml had higher fibulin-3 protein levels than untreated controls (p less than 0.05).
  • At 10 µg/ml, fluoro-edenite did not lead to a statistically significant change in fibulin-3 protein levels.
  • Fibulin-3 mRNA was increased in cells exposed to each of the three fluoro-edenite concentrations.
  • As with the protein results, cells exposed to the A, B, C and D volcanic particulates showed no statistically significant increase in fibulin-3 mRNA (data not shown).
  • In a public dataset, stathmin transcript (RNA) levels were significantly higher in lung tumors from patients exposed to asbestos (26 samples) than in tumors from patients not exposed.
• The authors' conclusion: The authors speculated that fibulin-3 overexpression and stathmin activation may be responsible for malignant transformation of mesothelial cells after exposure to asbestos-like fibers.

Topics

Medical terms in this study, explained in our Lexicon: fluoro-edenite, Fibulin-3, Mesothelial Cells, Mesothelioma, Biancavilla, Biomarker, Lung Cancer, Malignant Transformation.

Related studies

• Mineral fibre toxicity: expression of retinoblastoma (Rb) and phospho-retinoblastoma (pRb) protein in alveolar epithelial and mesothelial cell lines exposed to fluoro-edenite fibres — G. Musumeci, V. Cardile, et al. (2011)
• Fibulin-3 immunoexpression in malignant mesothelioma due to fluoro-edenite: a preliminary report — R. Caltabiano, C. Loreto, et al. (2018)
• Fluoro-edenite and carbon nanotubes: The health impact of 'asbestos-like' fibres — E. Miozzi, V. Rapisarda, et al. (2016)
• Fluoro-edenite fibers induce expression of Hsp70 and inflammatory response — V. Cardile, L. Lombardo, et al. (2007)
• Angiogenesis correlates with macrophage and mast cell infiltration in lung tissue of animals exposed to fluoro-edenite fibers — G. Musumeci, C. Loreto, et al. (2016)
• Early effects of fluoro-edenite: correlation between IL-18 serum levels and pleural and parenchymal abnormalities — C. Ledda, C. Loreto, et al. (2016)

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