Inhibitors of cytoskeletal dynamics in malignant mesothelioma

• Type of Material: Article
• Authors: Katarina Reis, Karolinska Institutet; Jack Arbiser, Emory University; Anders Hjerpe, Karolinska Institutet; Katalin Dobra, Karolinska Institutet; Pontus Aspenström, Karolinska Institutet
• Language: English
• Date: 2020-12-15
• Publisher: Impact Journals, LLC.
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Reis et al.
• License: Creative Commons Attribution 3.0 IGO License
• Final Published Version (URL): http://dx.doi.org/10.18632/ONCOTARGET.27843
• Title of Journal or Parent Work: Oncotarget
• Volume: 11
• Issue: 50
• Start Page: 4637
• End Page: 4647
• Grant/Funding Information: PA was supported by grants from Cancerfonden (CAN 2017/527), and KD was supported by grants from Cancerfonden (CAN 2015/479). JLA was supported by grants from NIH (RO1AR47901).
• Keywords: actin dynamics; malignant mesothelioma; vimentin; imipramine blue; cytoskeleton
• Research Categories: Health Sciences, Medicine and Surgery; Biology, General

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.