Cytoskeletal Organization Correlates to Motility and Invasiveness of Malignant Mesothelioma Cells

Our plain-English summary of Cytoskeletal Organization Correlates to Motility and Invasiveness of Malignant Mesothelioma Cells, by M. Keller, K. Reis, A. Hjerpe, et al (Cancers, 2021).

The study

• Authors: M. Keller, K. Reis, A. Hjerpe, K. Dobra, P. Aspenström
• Journal: Cancers
• Published: 2021;13(4)
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) is a rare but highly aggressive cancer that primarily originates from the pleura, peritoneum or pericardium. There is a well-established link between asbestos exposure and progression of MM. Direct invasion of the surrounding tissues is the main feature of MM, which is dependent on dysregulated communication between the mesothelium and the microenvironment. This communication is dependent on the dynamic organization of the cytoskeleton. We have analyzed the organization and function of key cytoskeletal components in MM cell lines of increasing malignancies measured as migratory and invasive properties, and we show that highly malignant and invasive MM cells have an organization of the actin filament and vimentin systems that is distinct from the less malignant MM cell lines. In addition, the Hippo tumor suppressor pathway was inactivated in the invasive MM cells, which was seen as increased YAP nuclear localization.

In plain English

This was a laboratory study of cells grown in dishes, not of people, and it did not study asbestos exposure. The authors compared seven malignant mesothelioma cell lines with one mesothelial cell line, MeT-5a, which they described as non-malignant while noting that it had been altered so it could keep growing in the laboratory. They stained the cells to examine their internal scaffolding (actin filaments, microtubules and vimentin filaments), their contacts with each other, and where a protein called YAP sat inside the cell. They also tested how well the cells closed scratch wounds, broke down a gel and invaded through a gel barrier. The cell lines differed markedly. ZL34 invaded far more (175 ± 15 cells, against 30 ± 23 for MeT-5a), closed wounds quickly and had more YAP in the nucleus (50 ± 6%, against 38 ± 3%). JL-1 and DM-3 broke down gel efficiently but barely invaded. The authors concluded that simple staining and tests could sort mesothelioma cell lines into categories. They put forward, as a hypothesis, that this might help diagnosis or prognosis.

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 comparing human cell lines grown in culture, using microscope staining and cell movement and invasion tests
• Who was studied: Eight human cell lines: MeT-5a (mesothelial, considered non-malignant), Mero-25 (described as epithelioid), DM-3 (sarcomatoid), and M-14-K, JL-1, STAV-AB, STAV-FCS and ZL34 (described as biphasic). Human BJ fibroblasts were used as a control for one test. The laboratories were in Uppsala and Stockholm, Sweden. No dates of the work are given.
• Exposure: No asbestos or other exposure was studied. The study compared features of different cell lines that already existed.
• Main results:
  • The ZL34 cells passed through a Matrigel barrier in much larger numbers (175 ± 15) than M-14-K (48 ± 19), STAV-AB (33 ± 12) and MeT-5a (30 ± 23).
  • JL-1 and DM-3 cells broke down gelatin efficiently but were more or less unable to pass through Matrigel (7 ± 6 and 4 ± 3 cells, respectively). STAV-AB also showed signs of breaking down the gel.
  • In the scratch-wound test, STAV-AB and ZL34 reached 80% wound density after 15.5 h and 18.5 h. MeT-5a took 44 h.
  • The share of YAP found in the nucleus was 38 ± 3% in MeT-5a. It was significantly higher in ZL34 (50 ± 6%) and significantly lower in JL-1 (18 ± 9%), STAV-FCS (21 ± 6%) and DM-3 (12 ± 5%).
  • Vimentin filaments took up 23 ± 5% of the cell body in MeT-5a. They took up a significantly larger area in ZL34 (48 ± 6%) and DM-3 (63 ± 12%).
  • Stable (acetylated) microtubules made up 48 ± 10% in MeT-5a. The share was high in Mero-25 (68 ± 8%), JL-1 (72 ± 7%) and DM-3 (78 ± 10%), and significantly lower in M-14-K (31 ± 10%) and ZL34 (34 ± 7%).
  • MeT-5a and Mero-25 cells were small and round (aspect ratio around 1.6). DM-3 cells were long (aspect ratio around 3.6), with long stress fibers.
• The authors' conclusion: The authors concluded that their data suggest mesothelioma cell lines can be sorted into separate categories using fairly simple cell staining and tests of cell shape and invasiveness. They hypothesized that this could potentially be used in diagnosis and/or prognosis.
• Limitations the authors state:
  • The comparison cell line MeT-5a is considered non-malignant, but the authors note it was immortalized by transfection with the SV40 large T antigen.
  • DM-3 cells could not be tested in the wound-closure test because they did not form confluent layers.

Topics

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Pleura, Peritoneum, Pericardium, Asbestos Exposure, Mesothelium.

Related studies

• Inhibitors of cytoskeletal dynamics in malignant mesothelioma — K. Reis, J.L. Arbiser, et al. (2020)
• CD70 expression correlates with a worse prognosis in malignant pleural mesothelioma patients via immune evasion and enhanced invasiveness — S. Inaguma, J. Lasota, et al. (2020)
• Alteration of cytoskeletal molecules in a human T cell line caused by continuous exposure to chrysotile asbestos — M. Maeda, Y. Chen, et al. (2013)
• Merlin, a "magic" linker between extracellular cues and intracellular signaling pathways that regulate cell motility, proliferation, and survival — I. Stamenkovic, Q. Yu (2010)
• 3-O-Methylfunicone, a metabolite produced by Penicillium pinophilum, modulates ERK1/2 activity, affecting cell motility of human mesothelioma cells — E. Buommino, I. Paoletti, et al. (2010)
• Mesothelioma cells breaking bad: loss of integrin α7 promotes cell motility and poor clinical outcomes in patients — D.J. Burkin, T.M. Fontelonga (2015)

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