The Epithelial-to-Mesenchymal Transition (EMT) in the Development and Metastasis of Malignant Pleural Mesothelioma

Our plain-English summary of The Epithelial-to-Mesenchymal Transition (EMT) in the Development and Metastasis of Malignant Pleural Mesothelioma, by V. Ramundo, G. Zanirato, E. Aldieri (International Journal of Molecular Sciences, 2021).

The study

• Authors: V. Ramundo, G. Zanirato, E. Aldieri
• Journal: International Journal of Molecular Sciences
• Published: 2021;22(22)
• Type of article: Review
• Cited by: 41 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive tumor mainly associated with asbestos exposure and is characterized by a very difficult pharmacological approach. One of the molecular mechanisms associated with cancer onset and invasiveness is the epithelial-to-mesenchymal transition (EMT), an event induced by different types of inducers, such as transforming growth factor β (TGFβ), the main inducer of EMT, and oxidative stress. MPM development and metastasis have been correlated to EMT; On one hand, EMT mediates the effects exerted by asbestos fibers in the mesothelium, particularly via increased oxidative stress and TGFβ levels evoked by asbestos exposure, thus promoting a malignant phenotype, and on the other hand, MPM acquires invasiveness via the EMT event, as shown by an upregulation of mesenchymal markers or, although indirectly, some miRNAs or non-coding RNAs, all demonstrated to be involved in cancer onset and metastasis. This review aims to better describe how EMT is involved in driving the development and invasiveness of MPM, in an attempt to open new scenarios that are useful in the identification of predictive markers and to improve the pharmacological approach against this aggressive cancer.

In plain English

This article was a review, not a new study. The authors summarized published research on the epithelial-to-mesenchymal transition (EMT), a process in which cells lose their typical surface-lining features and gain features linked to movement and invasion. They looked at its possible role in the development and spread of malignant pleural mesothelioma (MPM). The article did not describe how the studies it discussed were chosen. The review described earlier studies, mostly in cell lines and tumor samples, reporting that asbestos fibers can induce EMT in human mesothelial cells, including through a signaling protein called TGFβ and through oxidative stress. It also described reports that EMT markers such as Twist differed between MPM subtypes and were linked to prognosis. Other reports it described found that certain small RNA molecules (miRNAs) were expressed differently in sarcomatoid and biphasic MPM, and proposed TGFβ in pleural fluid as a possible diagnostic marker. The authors concluded that EMT is particularly crucial among the events involved in MPM onset and progression.

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: Narrative review of published research; no new data were collected and no method for selecting studies is described
• Who was studied: No study population of its own; the review discusses published laboratory studies (human mesothelial and mesothelioma cell lines, tumor samples, some animal studies) and clinical reports on malignant pleural mesothelioma
• Exposure: Asbestos fibers in general, described as serpentine (chrysotile) and amphibole (crocidolite, amosite, anthophyllite, actinolite and tremolite) forms; also EMT inducers such as TGFβ and oxidative stress
• Main results:
  • The review reported that several earlier studies showed asbestos can induce EMT, for example in human mesothelial cells exposed to asbestos fibers
  • The review cited a study reporting that asbestos fiber exposure induces EMT in human mesothelial cells through a TGF-β-mediated mechanism (via the SMAD pathway, leading to Twist, ZEB and Snail overexpression)
  • The review cited studies associating TGFβ pathway activation with MPM development
  • The review cited a report that hydrogen peroxide (an oxidative stress agent) can induce EMT in human mesothelial cells
  • The review described reports that in sarcomatoid MPM samples gamma-catenin is usually reduced while Vimentin and Twist are increased, a marker combination associated with prognostic value; Twist in MPM was associated with poor prognosis
  • The review described reports that some EMT-related miRNAs differ by MPM histotype, for example miR-199/214 overexpressed in sarcomatoid mesothelioma and miR-205 downregulated in biphasic and sarcomatoid MPM
  • The review described Klebe et al. as having shown elevated amosite asbestos fiber content by electron microscopy in sarcomatoid MPM samples
  • The review described TGFβ measured in patients' pleural effusion as a potential diagnostic marker for MPM, particularly combined with mesothelin and IL-10 levels
• The authors' conclusion: The authors concluded that, among events involved in MPM onset and progression, EMT is particularly crucial. In their view, it mediates the effects of asbestos fibers on human mesothelial cells through crosstalk between oxidative stress and TGFβ, with miRNAs also contributing, and these insights may help improve MPM diagnosis and treatment.

Topics

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

Medical terms in this study, explained in our Lexicon: Metastasis, Pleural Mesothelioma, Asbestos Exposure, Oxidative Stress, Mesothelium.

Related studies

• Epithelial to Mesenchymal Transition in Human Mesothelial Cells Exposed to Asbestos Fibers: Role of TGF-β as Mediator of Malignant Mesothelioma Development or Metastasis via EMT Event — S. Turini, L. Bergandi, et al. (2019)
• Multi-walled carbon nanotubes directly induce epithelial-mesenchymal transition in human bronchial epithelial cells via the TGF-β-mediated Akt/GSK-3β/SNAIL-1 signalling pathway — M. Polimeni, G.R. Gulino, et al. (2016)
• Prognostic significance of epithelial-mesenchymal transition in malignant pleural mesothelioma — A. Schramm, I. Opitz, et al. (2010)
• Epithelial-mesenchymal transition in malignant mesothelioma — A. Fassina, R. Cappellesso, et al. (2012)
• APE-1/Ref-1 Inhibition Blocks Malignant Pleural Mesothelioma Cell Proliferation and Migration: Crosstalk between Oxidative Stress and Epithelial Mesenchymal Transition (EMT) in Driving Carcinogenesis and Metastasis — V. Ramundo, G. Zanirato, et al. (2023)
• Blockage of epithelial to mesenchymal transition and upregulation of let 7b are critically involved in ursolic acid induced apoptosis in malignant mesothelioma cell — E.J. Sohn, G. Won, et al. (2016)

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