A new mosaic pattern in glioma vascularization: exogenous endothelial progenitor cells integrating into the vessels containing tumor-derived endothelial cells.

A new mosaic pattern in glioma vascularization: exogenous endothelial progenitor cells integrating into the vessels containing tumor-derived endothelial cells.
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胶质瘤血管化的新镶嵌模式:外源内皮祖细胞整合到含有肿瘤源性内皮细胞的血管中

DOI:
10.18632/oncotarget.1885
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发表时间:
2014-04-15
期刊:
影响因子:
--
通讯作者:
Zhang W
Zhang W
中科院分区:
其他
文献类型:
--
作者:
Chen X;Fang J;Wang S;Liu H;Du X;Chen J;Li X;Yang Y;Zhang B;Zhang W

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新出现的证据表明,胶质瘤干细胞样细胞(GSCs)转分化为血管内皮细胞(ECs)可能有助于肿瘤抵抗抗血管生成治疗。内皮祖细胞(Endothelial progenitor cells, EPCs)表现出积极的迁移和融入胶质瘤的新生血管,可能是传递基因以靶向GSCs转分化的良好载体。在C6胶质瘤大鼠模型中,我们发现了一种新的镶嵌模式,即外源性EPCs整合到含有肿瘤源性ECs的血管中。进一步,我们评估了这些归巢EPCs对C6胶质瘤细胞转分化的影响。C6胶质瘤细胞的转分化频率及GSCs转分化的关键因子HIF-1α、Notch1、Flk1在移植或未移植EPCs的胶质瘤中的表达无显著差异。此外,磁共振成像可以在体内追踪EPCs在胶质瘤中的迁移和结合,普鲁士蓝染色证实了这一点。从T2图谱中估计的磁标记EPCs的数量与流式细胞术直接测量的标记细胞计数有很好的相关性。综上所述,我们的研究结果可能为EPCs作为治疗和成像探针的未来应用提供合理的基础,以克服胶质瘤的抗血管生成耐药性并监测这种治疗的疗效。
Emerging evidence suggests that glioma stem-like cells (GSCs) transdifferentiating into vascular endothelial cells (ECs) possibly contributes to tumor resistance to antiangiogenic therapy. Endothelial progenitor cells (EPCs), showing active migration and incorporation into neovasculature of glioma, may be a good vehicle for delivering genes to target GSCs transdifferentiation. Here, we found a new mosaic pattern that exogenous EPCs integrated into the vessels containing the tumor-derived ECs in C6 glioma rat model. Further, we evaluated the effect of these homing EPCs on C6 glioma cells transdifferentiation. The transdifferentiation frequency of C6 glioma cells and the expressions of key factors on GSCs transdifferentiation, i.e. HIF-1α, Notch1, and Flk1 in gliomas with or without EPCs transplantation showed no significant difference. Additionally, magnetic resonance imaging could track the migration and incorporation of EPCs into glioma in vivo, which was confirmed by Prussian blue staining. The number of magnetically labeled EPCs estimated from T2 maps correlated well with direct measurements of labeled cell counts by flow cytometry. Taken together, our findings may provide a rational base for the future application of EPCs as a therapeutic and imaging probe to overcome antiangiogenic resistance for glioma and monitor the efficacy of this treatment.
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