uPA-uPAR系统对骨巨细胞瘤细胞p44(MAPK)信号转导的影响  

Effect of uPA-uPA system on p44 (MAPK) signal transduction in human giant cell tumor of bone

作　　者：徐若冰[1] 文剑明[2] 吕长海[3] 

机构地区：[1]广州医学院病理学教研室,广东广州510182 [2]中山大学中山医学院病理学教研室,广东广州510182 [3]中山大学附属口腔医院儿童牙科,广东广州510184

出　　处：《中国现代医学杂志》2005年第16期2430-2433,共4页China Journal of Modern Medicine

基　　金：教育部高等学校博士学科点专项科研基金资助项目(200046)

摘　　要：目的研究uPA/uPAR系统对骨巨细胞瘤细胞MAPK信号转导的影响。方法分离并培养骨巨细胞瘤细胞,用免疫组化检测骨巨细胞瘤组织中uPAR的表达水平,用免疫共沉淀方法检测外源激活或阻断uPA-uPAR对骨巨细胞瘤细胞信号转导通路的p44(MAPK)蛋白磷酸化水平的影响。结果仅有单核基质细胞可以在体外培养中长期生存;在骨巨细胞瘤组织中uPAR主要表达在部分单核基质细胞和一些多核巨细胞的胞膜上;将uPA-ATF加入培养的骨巨细胞瘤细胞后,细胞信号通路上的p44蛋白磷酸化水平明显增高。用uPAR抗体处理后,细胞p44蛋白磷酸化水平明显降低。说明uPA-ATF具有细胞信号转导活性,该活性受uPAR拮抗剂的影响。结论本实验检测到uPA-uPAR系统是通过p44(MAPK)信号转导通路转导信息,从而调节骨巨细胞瘤细胞增殖、分化及其他生物学行为。[Objective ] To study the effect of urokinase-type plasminogen activator （uPA）and its receptor（uPAR） system on p44（MAPK） signal transduction in giant cell tumor of bone （GCT）. [Methods] Expressions of uPAR in GCT tissue was detected by immunohistochemistry. Phosphorylation level of mitogen-activate protein kinase （P44） in uPA/uPAR signal pathway in cultured GCT cells was detected by immunoprecipetation. [Results] Only the mononuclear stromal cells can survive through in vitro; 2）Urokinase-type plasminogen activator receptor （uPAR） is positive on the cell membrane and in cytoplasm of some mononuclear stromal cells （MSCs） and muhinucleated giant cells （MGCs）; 3） After treatment by uPA-ATF, the phosphorylation level of P44 in GCT cultured cells is much higher than the control. Addition of anti-uPAR antibody in the cells remarkably down-regulated the phosphorylation level of P44 as compared with the control group, suggesting that uPA-ATF participates cell signal transduction and this reaction can be inhibited by anti-uPAR antibody. [Conclusion] The study demonstrates that uPA-uPAR system direcdy regulates the phosphorylation level of P44（MAPK） pathway

关 键 词：骨巨细胞瘤 尿激酶型纤溶酶原激活物 信号转导 

分 类 号：R738.2[医药卫生—肿瘤]