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.
Highlights
Living organisms are formed by a number of cell types that work together to maintain normal tissue homeostasis
There is a well-established link between asbestos exposure, release of reactive oxygen species (ROS) and inflammatory mediators, which collectively lead to malignant transformation of mesothelial cells and progression of MMs
We have recently developed new tools for in-vitro analysis of cytoskeletal dynamics that correlate to tumor cell differentiation, which remains to date the only reliable predictive marker of malignant MM aggressiveness
Summary
Living organisms are formed by a number of cell types that work together to maintain normal tissue homeostasis. This neatly organized collaboration is lost in cancers, primarily because several cell-types responsible for correct tissue homeostasis change their behavior [1]. These changes are associated with alterations in cell morphology and cell migration, which are regulated by the cytoskeleton [2]. There is a significant number of cases with unknown etiology, in particular with peritoneal MMs [4]
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