uPA系统在骨髓基质细胞—白血病细胞共培养模型中表达及意义研究

发布时间：2018-10-13 18:21

【摘要】：uPA系统包含尿激酶纤溶酶原激活物(urokinase type plasminogen activator,uPA)、尿激酶纤溶酶原激活物受体(urokinase type plasminogen activator receptor,uPAR/CD87)以及纤溶酶原激活物抑制剂(plasminogen activator inhibitors,PAI-1and PAI-2)。多种人类恶性肿瘤的局部侵袭和转移与uPA系统密切相关,是目前治疗肿瘤的重要分子靶点。本课题通过实时荧光定量PCR、ELISA等方法研究白血病人骨髓基质细胞-白血病细胞共培养中uPA、uPAR、PAI-1、MMP-9、VEGF的表达情况,从而探究白血病骨髓微环境与uPA系统之间的作用关系。研究结果表明,与骨髓基质细胞(bone marrow stromal cells,BMSCs)单独培养相比,在共培养条件下白血病骨髓基质细胞的uPA、uPAR、PAI-1、VEGF的表达显著升高,而共培养条件下白血病细胞HL60的MMP-9表达升高。co-BMSCs中的uPA、uPAR和PAI-1的表达显著升高可以进一步解释白血病细胞在骨髓微环境的生长、发展、复发以及白血病不良预后与uPA系统有密切的联系。共培养条件下HL60的MMP-9的表达升高,这或许可以解释为骨髓微环境有助于白血病细胞的扩散。
[Abstract]:The uPA system includes urokinase plasminogen activator (urokinase type plasminogen activator,uPA), urokinase plasminogen activator receptor (urokinase type plasminogen activator receptor,uPAR/CD87) and plasminogen activator inhibitor (plasminogen activator inhibitors,PAI-1and PAI-2). The local invasion and metastasis of various human malignant tumors are closely related to the uPA system and are important molecular targets for the treatment of cancer. The expression of uPA,uPAR,PAI-1,MMP-9,VEGF in the co-culture of leukemic human bone marrow stromal cells (BMSCs) and leukemic cells was studied by real-time fluorescence quantitative PCR,ELISA, so as to explore the relationship between leukemic bone marrow microenvironment and uPA system. The results showed that the expression of uPA,uPAR,PAI-1,VEGF in leukemic bone marrow stromal cells was significantly increased in co-culture compared with that in bone marrow stromal cells (bone marrow stromal cells,BMSCs) alone. The increased expression of uPA,uPAR and PAI-1 in co-BMSCs could further explain the growth and development of leukemic cells in bone marrow microenvironment. Recurrence and poor prognosis of leukemia are closely associated with uPA system. The increased expression of MMP-9 in HL60 may be explained by the fact that bone marrow microenvironment contributes to the proliferation of leukemic cells.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R733.7

【相似文献】