Cytoskeletal Organization Correlates to Motility and Invasiveness of Malignant Mesothelioma Cells

SIMPLE SUMMARY: The cytoskeleton is responsible for maintaining normal tissue homeostasis by a tight regulation of cell morphogenesis and cell migration. This homeostasis is lost in cancer mainly because alterations in cytoskeletal dynamics are leading to an increased migratory and invasive capacity of cancer cells. The organization of the cytoskeleton is by large an unknown factor in malignant mesothelioma; therefore we sought to examine the cytoskeletal dynamics and invasive properties of different malignant mesothelioma cell lines originating from patients. Our data suggest that it is possible to classify malignant mesothelioma cell lines into separate categories using straight forward cell staining and analysis of the morphological and invasive capacity of mesothelioma cells. Early diagnosis and new diagnostic tools are urgently needed to effectively treat patients and we propose that the analyses described in this article could potentially provide diagnostic tools that can be further tested on patients. 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.