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首页> 外文期刊>Journal of Cancer >Characterization of Cancer Stem-Like Cells Derived from Mouse Induced Pluripotent Stem Cells Transformed by Tumor-Derived Extracellular Vesicles
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Characterization of Cancer Stem-Like Cells Derived from Mouse Induced Pluripotent Stem Cells Transformed by Tumor-Derived Extracellular Vesicles

机译：肿瘤诱导的细胞外囊泡转化的小鼠诱导多能干细胞衍生的癌症干细胞样细胞的表征。

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Several studies have shown that cancer niche can perform an active role in the regulation of tumor cell maintenance and progression through extracellular vesicles-based intercellular communication. However, it has not been reported whether this vesicle-mediated communication affects the malignant transformation of normal stem cells/progenitors. We have previously reported that the conditioned medium derived from the mouse Lewis Lung Carcinoma (LLC) cell line can convert mouse induced pluripotent stem cells (miPSCs) into cancer stem cells (CSCs), indicating that normal stem cells when placed in an aberrant microenvironment can give rise to functionally active CSCs. Here, we focused on the contribution of tumor-derived extracellular vesicles (tEVs) that are secreted from LLC cells to induce the transformation of miPSCs into CSCs. We isolated tEVs from the conditioned medium of LLC cells, and then the differentiating miPSCs were exposed to tEVs for 4 weeks. The resultant tEV treated cells (miPS-LLCev) expressed Nanog and Oct3/4 proteins comparable to miPSCs. The frequency of sphere formation of the miPS-LLCev cells in suspension culture indicated that the self-renewal capacity of the miPS-LLCev cells was significant. When the miPS-LLCev cells were subcutaneously transplanted into Balb/c nude mice, malignant liposarcomas with extensive angiogenesis developed. miPS-LLCevPT and miPS-LLCevDT, the cells established from primary site and disseminated liposarcomas, respectively, showed their capacities to self-renew and differentiate into adipocytes and endothelial cells. Moreover, we confirmed the secondary liposarcoma development when these cells were transplanted. Taken together, these results indicate that miPS-LLCev cells possess CSC properties. Thus, our current study provides the first evidence that tEVs have the potential to induce CSC properties in normal tissue stem cells/progenitors.
机译：数项研究表明，癌症小生境可通过基于细胞外小泡的细胞间通讯在调节肿瘤细胞维持和进展中发挥积极作用。然而，尚未报道这种囊泡介导的通讯是否影响正常干细胞/祖细胞的恶性转化。我们以前曾报道过，源自小鼠Lewis Lewis肺癌（LLC）细胞系的条件培养基可以将小鼠诱导的多能干细胞（miPSC）转换为癌症干细胞（CSC），这表明将正常干细胞放在异常的微环境中可以产生功能活跃的CSC。在这里，我们集中于LLC细胞分泌的肿瘤源性细胞外囊泡（tEV）的贡献，以诱导miPSC转化为CSC。我们从LLC细胞的条件培养基中分离出tEV，然后将分化的miPSC暴露于tEV 4周。所得的经tEV处理的细胞（miPS-LLCev）表达与miPSC相当的Nanog和Oct3 / 4蛋白。在悬浮培养中miPS-LLCev细胞的球形形成频率表明，miPS-LLCev细胞的自我更新能力是显着的。当将miPS-LLCev细胞皮下移植到Balb / c裸鼠中时，发生了具有广泛血管生成的恶性脂肪肉瘤。 miPS-LLCevPT和miPS-LLCevDT，分别是从原发部位和弥散性脂肪​​肉瘤建立的细胞，显示出它们自我更新并分化为脂肪细胞和内皮细胞的能力。此外，当这些细胞被移植时，我们证实了继发性脂肪肉瘤的发展。综上所述，这些结果表明miPS-LLCev细胞具有CSC特性。因此，我们目前的研究提供了第一个证据，证明tEV具有在正常组织干细胞/祖细胞中诱导CSC特性的潜力。

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