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Clin Cancer Res:阻断MSC旁分泌活动可以抑制骨肉瘤发展

2017-07-19 Yara MedSci原创

该研究结果总体上表明TEMSC可以促进骨肉瘤的进展,为IL6-和TGFβ阻断剂作为骨肉瘤的新的治疗方案提供了基础。

人骨肉瘤是一种遗传异质性的恶性肿瘤,即使侵入性的化疗方案也会有预后不良。由于目前药物驱动的突变尚未建立,解剖骨肉瘤细胞和支持基质之间的互作可能为寻找新的治疗靶标提供新的视角。通过使用可以原位发光的异种移植骨肉瘤的小鼠模型,研究人员评估了肿瘤细胞外囊泡(EV)和培养的间充质干细胞(TEMSC)对骨肉瘤进展的影响。特征和功能研究被用于评估间充质干细胞(MSC)的发育机制。研究人员分析了独立的组织系列标来进一步证实临床发现,并利用体积排阻法分离了病人的血清EV并分析了其组成。结果显示:由恶性骨肉瘤细胞分泌的EV选择性的整合到膜相关形式的TGFβ, TGFβ可以诱导MSCs产生炎症性IL6。TEMSC能够促进肿瘤生长,并且伴随肿瘤内的STAT3的激活和肺转移形成,而且这些现象在对照的MSC中是没有观察到的。重要的是:静脉内施用抗IL-6受体抗体tocilizumab可以消除TEMSC的癌症促进作用。人的骨肉瘤组织RNA-Seq结果显示出明显的TGFβ诱导的促转移基因表达特征。人肉骨瘤的组织芯片免疫染色显示具有激活的STAT3信号,这与在TEMSC处理的小鼠中观察到的是一致的。最后,研究人员还从

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    2018-04-07 gwc392
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    2017-07-21 luominglian113

    学习了,谢谢分享

    0

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    2017-07-21 huanbaofeng
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    2017-07-21 lfcmxl
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    2017-07-20 虈亣靌

    学习了谢谢分享

    0

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    2017-07-20 ylzr123

    好文,值得点赞!认真学习,应用于实践!谢谢分享给广大同好!

    0

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    2017-07-19 130****4638

    学习了谢谢分享

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