Recruited Brain Tumor-Derived Mesenchymal Stem Cells Contribute to Brain Tumor Progression
Recruited Brain Tumor-Derived Mesenchymal Stem Cells Contribute to Brain Tumor Progression
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DOI：
10.1002/stem.1614
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发表时间：
2014-05-01
期刊：
影响因子：
5.2
通讯作者：
Badn, Wiaam
中科院分区：
文献类型：
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作者：
Behnan, Jinan;Isakson, Pauline;Badn, Wiaam
参与脑肿瘤结构和进展的细胞的身份仍不清楚。间充质干细胞（MSCs）最近从正常小鼠脑中分离出来。在这里，我们报告骨髓间质干细胞样细胞浸润到GL261小鼠胶质瘤模型中。这些脑肿瘤来源的间充质干细胞（BT-MSCs）被定义为表型（Lin-Sca-1+CD9+CD44+CD166+/-），并具有多能分化能力。我们发现BT-MSCs的浸润与肿瘤进展相关；此外，BT-MSCs还能提高GL261细胞的体外增殖率。我们首次报道了大多数GL261细胞在体外贴壁和球培养条件下表达间充质表型，并且非msc群体在体内是非致瘤性的。虽然GL261细胞系在体外表达间充质表型标记，但在接种绿色荧光蛋白（GFP）转基因小鼠的野生型GL261和接种野生型小鼠的GL261-GFP细胞中，大多数BT-MSCs都是从宿主来源募集的细胞。我们展示了趋化因子受体CXCR4和CXCR6在不同募集细胞群中的表达。在体内，GL261细胞改变了标记谱，获得了一种更类似于在球培养条件下生长的细胞的表型。最后，我们在人胶质母细胞瘤中确定了一个BT-MSC群体，在新鲜分离和培养扩增的细胞中都是CD44+CD9+CD166+。我们的数据表明，具有msc样表型的细胞浸润到肿瘤基质中，并在体外和体内肿瘤细胞生长中发挥重要作用。因此，我们建议靶向BT-MSCs可能是治疗胶质母细胞瘤患者的一种可能策略。干细胞2014；32:1110 - 1123
The identity of the cells that contribute to brain tumor structure and progression remains unclear. Mesenchymal stem cells (MSCs) have recently been isolated from normal mouse brain. Here, we report the infiltration of MSC-like cells into the GL261 murine glioma model. These brain tumor-derived mesenchymal stem cells (BT-MSCs) are defined with the phenotype (Lin-Sca-1+CD9+CD44+CD166+/-) and have multipotent differentiation capacity. We show that the infiltration of BT-MSCs correlates to tumor progression; furthermore, BT-MSCs increased the proliferation rate of GL261 cells in vitro. For the first time, we report that the majority of GL261 cells expressed mesenchymal phenotype under both adherent and sphere culture conditions in vitro and that the non-MSC population is nontumorigenic in vivo. Although the GL261 cell line expressed mesenchymal phenotype markers in vitro, most BT-MSCs are recruited cells from host origin in both wild-type GL261 inoculated into green fluorescent protein (GFP)-transgenic mice and GL261-GFP cells inoculated into wild-type mice. We show the expression of chemokine receptors CXCR4 and CXCR6 on different recruited cell populations. In vivo, the GL261 cells change marker profile and acquire a phenotype that is more similar to cells growing in sphere culture conditions. Finally, we identify a BT-MSC population in human glioblastoma that is CD44+CD9+CD166+ both in freshly isolated and culture-expanded cells. Our data indicate that cells with MSC-like phenotype infiltrate into the tumor stroma and play an important role in tumor cell growth in vitro and in vivo. Thus, we suggest that targeting BT-MSCs could be a possible strategy for treating glioblastoma patients. Stem Cells 2014;32:1110-1123