Inhibitors of cytoskeletal dynamics in malignant mesothelioma

Our plain-English summary of Inhibitors of cytoskeletal dynamics in malignant mesothelioma, by K. Reis, J.L. Arbiser, A. Hjerpe, et al (Oncotarget, 2020).

The study

• Authors: K. Reis, J.L. Arbiser, A. Hjerpe, K. Dobra, P. Aspenström
• Journal: Oncotarget
• Published: 2020;11(50):4637-4647
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesotheliomas (MMs) are highly aggressive mesenchymal tumors that originate from mesothelial cells lining serosal cavities; i.e., the pleura, peritoneum, and pericardium. Classically, there is a well-established link between asbestos exposure, oxidative stress, release of reactive oxygen species, and chronic inflammatory mediators that leads to progression of MMs. MMs have an intermediate phenotype, with co-expression of mesenchymal and epithelial markers and dysregulated communication between the mesothelium and the microenvironment. We have previously shown that the organization and function of key cytoskeletal components can distinguish highly invasive cell lines from those more indolent. Here, we used these tools to study three different types of small-molecule inhibitors, where their common feature is their influence on production of reactive oxygen species. One of these, imipramine blue, was particularly effective in counteracting some key malignant properties of highly invasive MM cells. This opens a new possibility for targeted inhibition of MMs based on well-established molecular mechanisms.

Copyright: © 2020 Reis et al.

In plain English

This was a laboratory study of cancer cells grown in dishes. It did not study patients or asbestos exposure. The authors used three human malignant mesothelioma cell lines (ZL34, STAV-AB and STAV-FCS), derived from pleural effusions of patients. They treated the cells with one of three compounds chosen because they affect reactive oxygen species: imipramine blue (0.5 micromolar), honokiol (20 micromolar) or Tris-dibenzylideneacetone-dipalladium (1 micromolar). Control cells received only the solvent, DMSO. After 20 hours of treatment, the authors examined the cells' internal scaffolding (the cytoskeleton) and attachment points under the microscope. They also followed scratch-wound closure in treated cells over 48 hours. In ZL34 cells, which the authors describe as highly invasive, imipramine blue caused loss of stress fibers in 69.0% of cells. It raised the cell area occupied by vimentin from 38.3% to 54.6% and lowered the nuclear fraction of the protein YAP from 46.7% to 40.0%. All three compounds slowed wound closure in ZL34 cells. Effects on STAV-AB cells were less prominent. The authors concluded that imipramine blue appeared the most effective compound, and that ZL34 cells were the most responsive.

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) experiment on human malignant mesothelioma cell lines treated with three small-molecule compounds, compared with vehicle (DMSO) controls
• Who was studied: Three human malignant mesothelioma cell lines (ZL34, STAV-AB, STAV-FCS), derived from pleural effusions of patients. STAV-AB is classified as epithelioid; STAV-FCS and ZL34 are classified as biphasic.
• Exposure: Treatment with imipramine blue (0.5 micromolar), honokiol (20 micromolar) or Tris-dibenzylideneacetone-dipalladium (1 micromolar), compared with DMSO only. Treatment lasted 20 hours for the microscopy analyses. Wound closure was followed for 48 hours with the compounds present. Asbestos itself was not studied; it is mentioned only as background.
• Main results:
  • In ZL34 cells, imipramine blue caused loss of stress fibers in 69.0% of cells. Small lamellipodia were seen in 22.0% of treated cells, compared with 70.3% of DMSO-treated cells.
  • In STAV-FCS cells, imipramine blue reduced the share of cells with stress fibers from 93.5% (DMSO control) to 21.0%.
  • In ZL34 cells, the cell area occupied by vimentin was 38.3% in controls and increased significantly to 54.6% with imipramine blue.
  • In ZL34 cells, imipramine blue lowered the nuclear fraction of YAP from 46.7% to 40.0%.
  • In the wound-closure assay, ZL34 cells were slowed by all three compounds, most of all by Tris-dibenzylideneacetone-dipalladium. STAV-FCS cells showed marked slowing with imipramine blue. Treated wound closure was shown over 48 hours.
  • In STAV-AB cells, the compounds had less prominent effects on cell shape and actin, and little or no slowing of wound closure.
• The authors' conclusion: The authors concluded that imipramine blue appeared to be the most effective of the three compounds at counteracting malignant properties of the mesothelioma cells. They added that the cell lines responded differently, with ZL34 cells the most responsive.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Mesenchymal Tumor, Mesothelial Cells, Pleura, Peritoneum, Pericardium, Asbestos Exposure, Oxidative Stress.

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