Fusion of cancer stem cells and mesenchymal stem cells contributes to glioma neovascularization.
Fusion of cancer stem cells and mesenchymal stem cells contributes to glioma neovascularization.
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DOI：
10.3892/or.2015.4135
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发表时间：
2015-10
期刊：
影响因子：
4.2
通讯作者：
Chao Sun;Dongliang Zhao;X. Dai;Jinsheng Chen;Xiaoci Rong;Haiyang Wang;Ai-dong Wang;Ming Li;Jun Dong;Qiang Huang;Q. Lan
中科院分区：
文献类型：
--
作者：
Chao Sun;Dongliang Zhao;X. Dai;Jinsheng Chen;Xiaoci Rong;Haiyang Wang;Ai-dong Wang;Ming Li;Jun Dong;Qiang Huang;Q. Lan
近年来，肿瘤细胞自主生成肿瘤血管的能力受到了相当大的关注。然而，自主权的程度是相对的。同时，骨髓间充质干细胞（BMSCs）对肿瘤新生血管形成的影响尚未完全阐明。本研究旨在阐明胶质瘤干细胞与骨髓间充质干细胞的融合是否参与胶质瘤新生血管的形成。从转基因裸鼠中分离骨髓间充质干细胞，其中所有有核细胞表达绿色荧光蛋白（GFP）。证实了BMSC的免疫表型和多向分化潜能。用红色荧光蛋白转染SU 3胶质瘤干/祖细胞（SU 3-RFP细胞）。在BMSC-GFP和SU 3-RFP共培养体系中，流式细胞仪检测RFP+/GFP+细胞，并通过双色分离。在体内和体外测定RFP+/GFP+细胞的血管生成作用。流式细胞仪分析显示，BMSC表达高水平的CD 105，C44，和非常低水平的CD 45和CD 11b。当与SU 3-RFP共培养时，共表达RFP和GFP的细胞中73.8%在第5代被鉴定为融合细胞。融合细胞在体外表现出管状形成能力，在体内可产生实体瘤并形成肿瘤血管。在可移植的异种移植胶质瘤的双色原位模型中，表达CD 105、RFP和GFP的黄色血管样结构被鉴定为源自融合细胞的新生血管。在荷瘤小鼠中观察到的黄色血管直接来自BMSC和SU 3-RFP细胞的融合。因此，细胞融合是肿瘤新生血管形成的驱动因素之一。
The ability of tumor cells to autonomously generate tumor vessels has received considerable attention in recent years. However, the degree of autonomy is relative. Meanwhile, the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on tumor neovascularization has not been fully elucidated. The present study aimed to illuminate whether cell fusion between glioma stem cells and BMSC is involved in glioma neovascularization. BMSCs were isolated from transgenic nude mice, of which all nucleated cells express green fluorescent protein (GFP). The immunophenotype and multilineage differentiation potential of BMSC were confirmed. SU3 glioma stem/progenitor cells were transfected with red fluorescent protein (SU3-RFP cells). In a co-culture system of BMSC-GFP and SU3-RFP, RFP+/GFP+ cells were detected and isolated by dual colors using FACS. The angiogenic effect of RFP+/GFP+ cells was determined in vivo and in vitro. Flow cytometry analysis showed that BMSC expressed high levels of CD105, C44, and very low levels of CD45 and CD11b. When co-cultured with SU3-RFP, 73.8% of cells co-expressing RFP and GFP were identified as fused cells in the 5th generation. The fused cells exhibited tube formation ability in vitro and could give rise to a solid tumor and form tumor blood vessels in vivo. In the dual-color orthotopic model of transplantable xenograft glioma, yellow vessel-like structures that expressed CD105, RFP and GFP were identified as de novo-formed vessels derived from the fused cells. The yellow vessels observed in the tumor-bearing mice directly arose from the fusion of BMSCs and SU3-RFP cells. Thus, cell fusion is one of the driving factors for tumor neovascularization.