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

恶性胸膜间皮瘤生长和侵袭机制分析：在病理诊断中的应用及新疗法的开发

• 批准号: 23590438
• 负责人: TSUJIMURA Tohru
• 金额: $ 3.41万
• 依托单位: Hyogo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590438/
• 关键词: 悪性胸膜中皮腫; 上皮間葉転換; 浸潤; Polycomb遺伝子群; EZH2; 予後

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.

恶性间皮瘤以胸腔内弥漫性生长和胸壁浸润性增生为特征，导致预后不良。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瘤细胞之间的基因表达谱。我们发现，EZH 2，这有助于靶基因的表观遗传沉默，在恶性间皮瘤中的表达水平高于间皮瘤细胞。当间皮瘤细胞中的EZH 2表达通过引入EZH 2-siRNA而被抑制时，这些细胞的增殖降低。对恶性间皮瘤手术标本中EZH 2表达的免疫组化分析显示，EZH 2的高表达与患者的总生存期较短相关。恶性间皮瘤的生物学特性，如向胸腔内生长和向胸壁侵犯，可能与表观遗传学有关。

项目成果

Circulating tumor cell (CTC) as a significant clinical marker in epithelioid-type malignant pleural mesothelioma (MPM)

循环肿瘤细胞（CTC）作为上皮样型恶性胸膜间皮瘤（MPM）的重要临床标志物

• 发表时间: 2012
• 作者: Yoneda K;Sato A;Tsujimura T et al(全15名)
• 通讯作者: Tsujimura T et al(全15名)

Circulating endothelial cell (CEC), a surrogate of tumor angiogenesis, as a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM)

循环内皮细胞 (CEC) 是肿瘤血管生成的替代物，可作为恶性胸膜间皮瘤 (MPM) 的诊断和预后标志物

• 发表时间: 2011
• 作者: Yoneda K;Sato A;Tsujimura T et al(全15名)
• 通讯作者: Tsujimura T et al(全15名)

TGF-β synergizes with defects in the Hippo pathway to stimulate human malignant mesothelioma growth.

• DOI: 10.1084/jem.20111653
• 发表时间: 2012-03-12
• 期刊: The Journal of experimental medicine
• 作者: Fujii M;Toyoda T;Nakanishi H;Yatabe Y;Sato A;Matsudaira Y;Ito H;Murakami H;Kondo Y;Kondo E;Hida T;Tsujimura T;Osada H;Sekido Y
• 通讯作者: Sekido Y

肉腫型悪性胸膜中皮腫の細胞学的検討

肉瘤型恶性胸膜间皮瘤的细胞学研究

• 发表时间: 2011
• 作者: 鳥居良貴;石田誠実;辻村亨;他(全9名)
• 通讯作者: 他(全9名)

Differential diagnosis of malignant pleural mesothelioma and reactive mesothelium in pleural effusion cytology -molecular biological approach

恶性胸膜间皮瘤与胸水反应性间皮细胞学鉴别诊断-分子生物学方法

• 发表时间: 2012
• 作者: Saito T;Ryu M;Fukumura Y;Asahina M;Arakawa A;Nakai K;Miura H;Saito M;Yao T;Tsujimura T.
• 通讯作者: Tsujimura T.