TGF-β1通路调控MET在滑膜肉瘤双相分化和侵袭转移中作用及机制

项目名称： TGF-β1通路调控MET在滑膜肉瘤双相分化和侵袭转移中作用及机制

项目编号： No.81202120

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 齐妍

作者单位： 石河子大学

项目金额： 23万元

中文摘要： 上皮间叶转化（EMT/MET）与肿瘤的侵袭、转移密切相关，涉及TGF-β1等通路和转录因子调控。但间叶源性肿瘤中EMT/MET的研究少见。滑膜肉瘤（SS）是一种组织起源不明、具有上皮和间叶双相分化的软组织肉瘤，90%患者死于转移。SS双相分化的形态特征和高侵袭性的临床经过为系统地探讨TGF-β1介导MET/EMT发生及与融合基因SYT-SSX的关系提供了良好模型。本研究拟在免疫组化等技术检测SS组织和细胞株中TGF-β1通路与MET/EMT相关分子和融合基因表达基础上，运用激光显微切割结合RT-PCR和CGH/ArrayCGH，分别检测SS上皮和间叶两种成分中以上指标表达及染色体基因组改变；在SS细胞株中干预TGF-β1表达，检测干预前后细胞形态及以上指标的变化，探讨TGF-β1通路调控EMT/MET在SS双相分化和侵袭转移中的作用机制及与融合基因的关系，为SS的治疗和预后评估提供新靶点。

中文关键词： 滑膜肉瘤；外显子芯片；上皮间质转化；TGF-β1信号通路；侵袭和迁移

英文摘要： Epithelial-mesenchymal transition (EMT/MET) is closely associated with the invasion and metastasis of cancer, and involved in the regulation of TGF-β1 signaling pathway and transcription factors. On the other hand, TGF-β1 is also an important inducer of EMT. However, the role of EMT/MET in sarcoma progression is considerably less well understood. Synovial sarcoma (SS) is a malignant tumor of the soft tissue characterized by uncertain histological origin and has biphasic morphology of mesenchyme and epithelium. Clinical outcomes of SS are very poor and approximately 90% of patients die from metastatic disease. The biphasic morphology and high invasiveness of SS make it a good model for investigating the relationship between TGF-β1-induced EMT/MET and fusion gene SYT-SSX. The study will then separate epithelium and mesenchyme from SS tissues using laser microdissection technique; analyze the expression of TGF-β1 and EMT related markers by RT-PCR; and detect genomic alterations using CGH or Array CGH technique, respectively. This study will first analyze the expression of TGF-β1 pathway and EMT related markers, and fusion gene SYT-SSX in the epithelium and mesenchyme from SS tissues using laser microdissection technique. Furthermore, we will use a specific TGF-β1 inhibitor or inducer to treat SS cells and examine t

英文关键词： Synovial sarcomas；Human exome SNP chip；EMT；TGF-β1 signaling pathway；Motility and invasion