Keller Maureen, Reis Katarina, Hjerpe Anders, Dobra Katalin, Aspenström Pontus
Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, Sweden.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Cancers (Basel). 2021 Feb 8;13(4):685. doi: 10.3390/cancers13040685.
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.
恶性间皮瘤(MM)是一种罕见但极具侵袭性的癌症,主要起源于胸膜、腹膜或心包膜。石棉暴露与MM的进展之间存在已明确的联系。直接侵犯周围组织是MM的主要特征,这依赖于间皮细胞与微环境之间失调的通讯。这种通讯依赖于细胞骨架的动态组织。我们分析了以迁移和侵袭特性衡量的恶性程度不断增加的MM细胞系中关键细胞骨架成分的组织和功能,并且我们表明,高恶性和侵袭性的MM细胞具有与低恶性MM细胞系不同的肌动蛋白丝和波形蛋白系统组织。此外,侵袭性MM细胞中的Hippo肿瘤抑制通路失活,表现为YAP核定位增加。