Inhibitors of cytoskeletal dynamics in malignant mesothelioma
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Katarina Reis1, Jack L. Arbiser2, Anders Hjerpe3, Katalin Dobra3 and Pontus Aspenström1,4
1 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
2 Department of Dermatology, Emory University School of Medicine, Atlanta Veterans Administration Medical Center, Atlanta, GA, USA
3 Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Huddinge, Stockholm, Sweden
4 Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
|Pontus Aspenström,||email:||[email protected]|
Keywords: malignant mesothelioma; actin dynamics; vimentin; cytoskeleton; imipramine blue
Received: October 20, 2020 Accepted: November 30, 2020 Published: December 15, 2020
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.
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