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Mesenchymal stem cell-derived exosomes facilitate nasopharyngeal carcinoma progression

机译:间充质干细胞来源的外泌体促进鼻咽癌的进展

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摘要

Mesenchymal stem cells (MSCs), which are capable of differentiating into multiple cell types, are reported to exert multiple effects on tumor development. However, the relationship between MSCs and nasopharyngeal carcinoma (NPC) cells remains unclear. Exosomes are small membrane vesicles that can be released by several cell types, including MSCs. Exosomes, which can carry membrane and cytoplasmic constituents, have been described as participants in a novel mechanism of cell-to-cell communication. In the present study, we investigated the mechanisms underlying the interaction between MSCs and NPC cells. The data showed that MSCs secreted 40-100 nm heterogeneous small vesicles, which were defined as exosomes. Incubation of NPC cells with MSC-derived exosomes resulted in the uptake of exosomes by the cells, which promoted their proliferation, migration and tumorigenesis. After an extended treatment duration, the tumor cells showed morphological changes and significant changes in the expression of epithelial-mesenchymal transition (EMT) markers. Moreover, we found that FGF19 was highly expressed in MSC-exosomes and that exosomes stimulated NPC progression by activating the FGF19-FGFR4-dependent ERK signaling cascade and by modulating the EMT. All of these data indicated that exosomes participate in a novel mechanism by which MSCs influence NPC progression.
机译:据报道,能够分化为多种细胞类型的间充质干细胞(MSC)对肿瘤的发展产生多种影响。但是,MSC与鼻咽癌(NPC)细胞之间的关系仍不清楚。外泌体是小的膜囊泡,可以通过多种细胞类型(包括MSC)释放。可以携带膜和胞质成分的外来体已被描述为细胞间通讯新机制的参与者。在本研究中,我们调查了MSC和NPC细胞之间相互作用的潜在机制。数据显示,MSC分泌40-100 nm异质小囊泡,被定义为外泌体。 NPC细胞与MSC衍生的外泌体一起孵育导致细胞吸收外泌体,从而促进了它们的增殖,迁移和肿瘤发生。经过延长的治疗时间后,肿瘤细胞在上皮-间质转化(EMT)标志物的表达中表现出形态学变化和显着变化。此外,我们发现FGF19在MSC外泌体中高表达,并且外泌体通过激活FGF19-FGFR4依赖性ERK信号级联反应并调节EMT来刺激NPC进程。所有这些数据表明,外泌体参与了一种新的机制,MSC通过这种机制影响NPC的进程。

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