人骨肉瘤细胞致瘤性与临床预后关系的实验研究

Relationship between oncogenicity of human osteosarcoma cells and clinical prognosis

目的通过建立稳定的骨肉瘤体内模型,初步筛选出骨肉瘤的高致瘤性细胞群,分析骨肉瘤的致瘤性与临床患者预后的相关性。方法利用骨肉瘤患者的原代活组织检查标本及化疗后行保肢术或截肢术时所取的标本,接种裸鼠或非肥胖糖尿病/严重联合免疫缺陷(NOD/SCID)小鼠,致瘤后分离移植瘤,体内接种连续传代建立的骨肉瘤体内模型;应用流式细胞仪分析高致瘤骨肉瘤细胞表型,并对患者进行随访,统计其生存情况,了解骨肉瘤细胞的致瘤性与患者临床预后的关系。结果成功建立可稳定传代的人骨肉瘤小鼠体内模型,致瘤组预后差者占9/12,显著高于非致瘤组的3/18(P<0.01);致瘤性与患者复发、转移及死亡呈正相关(r=0.773,P=0.01)。移植瘤细胞中间充质干细胞标志CD44、CD90、CD166均呈高表达,分别为(56.1±2.0)%、(60.3±2.1)%、(61.4±4.1)%。结论高致瘤骨肉瘤患者的预后较非致瘤者差;CD44、CD90、CD166可作为临床判断骨肉瘤患者预后的指标。

Objective To build up a stable mouse model of human osteosarcoma,to screen cell mass with high oncogenicity,and to analyze the correlation between tumorigenesis and prognosis for osteosarcoma patients. Methods Nude mice or nonobese diabetic/severe combined immunodeficiency（NOD/SCID） mice were inoculated with the tumor specimens,which were obtained from the biopsy and operation in osteosarcoma patients.The phenotypes of the osteosarcoma cells were analyzed by flow cytometry.And the patients were followed up in order to analyze the survivorship and relationship between the tumorigenesis and clinical prognosis. Results Stable mouse models of human osteosarcoma were successfully constructed.The prognosis of mice in tumorigenesis group（9/12） was significantly worse than that in non-tumorigenesis group（3/18,P0.01）.The oncogenicity was positively correlated with relapse,metastasis and death（r=0.773,P=0.01）.CD44,CD90 and CD166 were highly expressed in mesenchymal stem cells in transplanted tumors（[56.1±2.0]%,[60.3±2.1]% and [61.4±4.1]%）. Conclusion Osteosarcoma patients with high oncogenicity have worse clinical prognoses.CD44,CD90 and CD166 can be used as prognostic indicators for the patients with osteosarcoma.