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Cell Death Dis:胃癌来源的间充质干细胞触发M2巨噬细胞极化促进胃癌转移

2019-12-22 QQY MedSci原创

肿瘤微环境中的固有巨噬细胞在肿瘤的发生发展过程中起着双重作用。迄今为止,肿瘤内巨噬细胞产生的机制仍未明确。在本研究中,研究人员在巨噬细胞耗竭的移植瘤小鼠模型中发现,巨噬细胞在胃癌来源的间充质干细胞(GC-MSCs)促瘤作用中起着重要作用。在胃癌组织中,证实了Ym-1、Fizz-1、arginase-1和CCR-2高表达,而iNOS低表达;而且通过双重免疫组化实验观察到GC-MSC和TAMs(肿瘤相

肿瘤微环境中的固有巨噬细胞在肿瘤的发生发展过程中起着双重作用。迄今为止,肿瘤内巨噬细胞产生的机制仍未明确。

在本研究中,研究人员在巨噬细胞耗竭的移植瘤小鼠模型中发现,巨噬细胞在癌来源的间充质干细胞(GC-MSCs)促瘤作用中起着重要作用。在癌组织中,证实了Ym-1、Fizz-1、arginase-1和CCR-2高表达,而iNOS低表达;而且通过双重免疫组化实验观察到GC-MSC和TAMs(肿瘤相关巨噬细胞)共定位。从胃癌组织中分离出的TAMs主要为M2型。

在共培养系统中,体外M2相关蛋白的表达、M2样免疫表型和GC-MSCs巨噬细胞的细胞因子谱证实了GC-MSCs对巨噬细胞极化的促进作用。

通过中和抗体阻断IL-6 /IL-8可显著减弱GC-MSC对M2样巨噬细胞极化的促进作用,而这一作用主要是由JAK2 / STAT3信号介导的。此外,GC-MSC相关巨噬细胞可促进胃癌细胞的转移和侵袭作用,还可显著增强胃癌细胞的EMT进程。

综上所述,该研究主要揭示了促癌的GC-MSC细胞通过分泌大量的IL-6和IL-8来促进胃癌微环境中M2巨噬细胞的极化,而这些GC-MSC相关的巨噬细胞随后可通过促进胃癌细胞的EMT进程进而促进胃癌细胞转移。

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    2020-01-29 维他命
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    2019-12-25 独孤立克

    干细胞是热点,但是进入临床仍然需要时间和临床疗效验证哦

    0

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    2019-12-24 cy0328
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