胶质瘤干祖细胞与骨髓间充质干细胞融合驱动肿瘤的血管形成  

Tumor angiogenesis promoted by fusion of glioma stem/progenitor cells with bone marrow mesenchymal stem cells

作　　者：赵东亮[1] 代兴亮[1] 孙超[1] 陈金生[1] 荣孝慈 王海洋[1] 王麒龙 芮琴[2] 王爱东[2] 王中勇[1] 董军[1] 兰青[1] 黄强[1] 

机构地区：[1]苏州大学附属第二医院神经外科,215004 [2]苏州大学附属第二医院实验中心

出　　处：《中华肿瘤杂志》2015年第5期336-341,共6页Chinese Journal of Oncology

基　　金：国家自然科学基金（81172400、81272799、81472739）;江苏省普通高校研究生科研创新计划（CXLX12-0843）;苏州市科技发展计划指导项目（SYS201477、SYSD2012090）

摘　　要：目的探讨在肿瘤血管生成过程中骨髓间充质干细胞（MSCs）与肿瘤细胞融合反应形成肿瘤血管的驱动作用。方法取转染红色荧光蛋白（RFP）基因的人脑胶质瘤干祖细胞SU3-RFP与转染绿色荧光蛋白（GFP）基因的绿色裸小鼠MSCs，进行体外共培养。将SU3-RFP细胞接种于绿色裸小鼠脑内形成移植瘤，在荧光显微镜和共聚焦显微镜下分别观察共培养细胞和移植瘤组织中RFP’／GFP’细胞或血管。结果MSCs在体外连续传代培养5代，高增殖活性基本不变，并高表达CDl05。在绿色裸小鼠股骨组织、移植瘤组织和临床胶质瘤组织中的肿瘤细胞和血管细胞均可表达CDl05。随着MSCs与SU3-RFP细胞共培养时间的延长和传代次数的增加，RFP’／GFP’黄色细胞的比例明显增加。流式细胞仪检测显示，RFP’／GFP’黄色细胞占83．7％。移植瘤组织压片及组织切片中可见血管壁基质在内的成束RFP’／GFP’黄色血管样结构及黄色血管横断面管壁结构，为MSCs与SU3-RFP融合细胞衍生的血管。结论肿瘤细胞与宿主MSCs发生融合，并驱动了肿瘤血管生成。Objective The aim of this study was to clarify whether the fusion of bone marrow mesenchymal stem cells （MSCs） with tumor cells can promote tumor angiogensis. Methods Human glioma stem/progenitor cells （GSPCs） （SU3 cells） were transfected with red fluorescent protein （RFP） gene. Bone marrow mesenchymal stem cells （MSCs） were harvested from nude mice with whole-body green fluorescent protein （GFP） gene expression. Then the two kinds of cells were co-cultured in vitro. At the same time SU3- RFP was transplanted into the brain of GFP-expressing nude mice to establish xenograft tumors. The co- cultured cells, GFP/RFP double positive （yellow） cells and blood vessels obtained from the xenograft tumors were observed under fluorescent microscope and laser scanning con_focal microscope. Results After five passages in vitro, MSCs maintained the proliferative activity and highly expressed CDI05. CDI05 was also expressed in the femurs of GFP-expressing nude mice, tumor cells, blood vessels of SU3 xenograft tumors, and clinical malignant gliomas. When MSCs were co-cultured with SU3-RFP, the ratio of yellow cells co-expressing RFP and GFP was significantly increased after extended time and continuous passages. According to the flow cytometry, yellow cells co-expressing RFP and GFP were 83.7% of the cultured cells. In tissue slices of the xenograft tumors, bundles of yellow vessel-like structure and cross-sectioned yellow vascular wall structures including vascular wall stroma cells were observed with RFP and GFP expression, and were identified as de novo formed vessels derived from fusion of MSCs with SU3-RFP cells. Conclusion Cell fusion occurs between tumor cells and host MSCs and it promotes tumor angiogenesis.

关 键 词：神经胶质瘤 细胞融合 干细胞 间充质干细胞 肿瘤血管生成 CD105 

分 类 号：R739.41[医药卫生—肿瘤]