Analysis of mechanisms by which malignant pleural mesothelioma grows and invades: application to pathological diagnosis and development of a new therapy

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Malignant mesothelioma is characterized by diffuse growth in the thoracic cavity and invasive proliferation in the chest wall, leading to poor prognosis. To clarify the mechanism by which malignant mesothelioma develops these features, we compared the gene expression profiling between malignant mesothelioma and mesothelial cells. We found that EZH2, which contributes to epigenetic silencing of target genes, was expressed at higher levels in malignant mesothelioma than in mesothelial cells. When EZH2 expression in mesothelioma cells was suppressed by the introduction of EZH2-siRNA, proliferation of these cells decreased. Immunohistochemical analysis of EZH2 expression in surgical specimens of malignant mesothelioma revealed correlation between higher expression of EZH2 and shorter overall survival of patients. It seems that epigenetics participates in biological characteristics of malignant mesothelioma, such as the growth in the thoracic cavity and the invasion into the chest wall.