骨源性肉瘤干细胞特征化表型和miRNA调控的实验研究

项目名称： 骨源性肉瘤干细胞特征化表型和miRNA调控的实验研究

项目编号： No.30872967

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 王晋

作者单位： 中山大学

项目金额： 30万元

中文摘要： 骨源性肉瘤是骨骼系统最常见的恶性肿瘤，新辅助化疗和广泛性切除使五年生存率接近60%。肿瘤干细胞(CSCs)是被包埋于结构复杂的肿瘤基质和血管网络之中，这类数量极少的细胞具有自我更新、增殖和多向分化等特性；miRNA 在干细胞分化和个体发育过程中，发挥极其重要的调控作用；CSCs生物学特性使其容易逃逸细胞毒药物的杀伤作用和机体免疫细胞的攻击，传统治疗后的复发与转移成为需要解决的主要问题。本课题拟通过肉瘤细胞学分离SP侧群细胞、培养Sacrospheres和建立NOD/SCID小鼠移植瘤模型；然后研究成瘤性CSCs、转移性CSCs与正常骨髓间充质干细胞的生物学特性和miRNA调控机制，寻找CSCs特征化表型和miRNA调控的靶点；进一步应用RNA干扰技术沉默靶点，观察小鼠体内效果。课题旨在探索选择性杀灭CSCs 而不损伤正常干细胞池的分子靶向型治疗，联合传统治疗，为骨源性肉瘤的治愈带来希望。

中文关键词： 骨源性肉瘤;骨肉瘤;肿瘤干细胞;miRNA

英文摘要： Osteogenic sarcoma is the most common primary bone malignancy of childhood and adolescence. Despite of advances in neo-adjuvant chemotherapy and aggressive surgery during the last 30 years, five-year survival rate has unsatisfactorily remained approximately 60%. The emerging Cancer Stem Cell hypothesis may provide a powerful tool to study biology of the Osteogenic sarcoma. Up to now, accumulating evidences have been in favor of the hypothesis postulating that tumors are initiated and maintained by a small subpopulation of cancer cells called Cancer Stem Cells (CSCs). CSCs, possessing "stem-like" characteristics such as self-renewal, pluripotence and unlimited proliferation, reside in a complicated environment consisted of complex tumor stroma and vascular network. These biological characteristics of CSCs facilitate evasion of cytotoxicity and immune attack. Recent studies have shown the key role of miRNA in differentiation of stem cells and ontogenesis. In this study, we plan to perform isolation of side population, culture of sacrospheres and establishment of xenograft model in NOD/SCID mouse. With the aim to find out characteristic phenotype and the miRNA regulation target of osteogenic sarcomas stem cells, we are to compare biological characteristics and regulation mechanism of miRNA among tumorogenic CSCs, metastatic CSCs and normal bone marrow mesenchymal stem cells.

英文关键词： osteogenic sarcoma;osteosarcoma; cancer stem cell; miRNA