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

恶性间皮瘤以胸腔弥漫性生长和胸壁侵袭性增殖为特征，预后不良。为了阐明恶性间皮瘤发展这些特征的机制，我们比较了恶性间皮瘤和间皮细胞之间的基因表达谱。我们发现EZH2在恶性间皮瘤中的表达水平高于间皮细胞，EZH2有助于表观遗传沉默靶基因。当EZH2-siRNA的导入抑制间皮瘤细胞中EZH2的表达时，这些细胞的增殖能力下降。恶性间皮瘤手术标本中EZH2表达的免疫组织化学分析显示，EZH2的高表达与患者总生存期缩短有关。表观遗传学似乎参与了恶性间皮瘤的生物学特性，如胸腔内的生长和胸壁的侵袭。

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.