Nature:人体“杀菌神器”如何变成癌症转移“帮凶”,有望阻止癌症扩散

2020-06-17 生物探索 生物探索

中性粒细胞如何向癌细胞“倒戈”?

中性粒细胞是一种免疫细胞,可为人体提供抵御感染的第一道防线。然而,这道防线有时候也不那么“牢固”,因为中性粒细胞也具有促进癌细胞转移的能力,有时候可能会向癌细胞“倒戈”。

6月11日,中国科学院院士、中山大学孙逸仙纪念医院院长宋尔卫教授团队在顶级期刊《Nature》在线发表了一项研究报告,揭示了中性粒细胞帮助癌细胞转移扩散的特殊机制。

https://doi.org/10.1038/s41586-020-2394-6

2004年,科研人员首次发现,中性粒细胞能够在胞外形成网状结构(NET)。这是一个DNA网络,包裹在对微生物有毒的酶中,可以捕获并杀死入侵的微生物。不过,越来越多证据表明,NETs也会参与肿瘤向远处转移的过程中去。一个有助于癌细胞扩散的过程。

为了揭开中性粒细胞帮助肿瘤转移扩散的机制,研究人员首先评估了544名乳腺癌患者的原发性和转移性肿瘤中的NET,发现在肿瘤转移之前,肝脏中就会出现大量的中性粒细胞浸润。

同时,研究人员还观察到,癌细胞表面存在一种被称为“CCDC25”的受体,能够以高特异性和亲和力与NET DNA结合,使NET成为肿瘤细胞的趋化因子,将乳腺、结肠等处的癌细胞“吸引”至肝脏中,形成新的肿瘤。

宋尔卫说:“如果通过影像学的方法,在乳腺癌还没有发生转移的时候,就检测到患者的肝脏中已经有大量的中性粒细胞群,就说明他发生肝转移的风险很高。”

在进一步实验中,CCDC25显示了从体外培养的人乳腺癌细胞中去除癌细胞的能力。与仍存在CCDC25的小鼠相比,用脂多糖分子(LPS)诱导炎症治疗后,从小鼠癌细胞表面清除CCDC25可显着减少肝转移和肺转移的发生。

在报告的最后,研究人员揭示了肿瘤细胞是如何从这种与网络的相互作用中获利的。他们用CCDC25作为生物化学技术中的“诱饵”,从癌细胞中筛选出CCDC25相互作用的蛋白质,从而鉴定出一种蛋白-整合素连接激酶(ILK),它能够调节细胞迁移和增殖等过程。当ILK被移除或其下游信号伙伴β-parvin蛋白被禁用时,癌细胞的生长和体外运动受到严重损害,并且在小鼠中,转移到肝脏的情况减少。

英国Francis Crick研究所的Emma Nolan和Ilaria Malanchi发表在《Nature》的同期文章中评论称,这项研究代表了遏制癌症扩散的关键进展,或将有助于研究人员制定一种特定的策略来阻止NET促进癌症转移。另外,文中所提供的数据也指出了通过监测血液中的NET DNA来预测肝转移的可能方法。当然,目前仍需进一步的研究来评估靶向CCDC25进行抗癌治疗的可行性。

原始出处:

Emma Nolan, Ilaria Malanchi. Neutrophil ‘safety net’ causes cancer cells to metastasize and proliferate. Nature, 2020.

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    2020-08-27 14818eb4m67暂无昵称

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    2021-04-13 liye789132251
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    2020-06-19 hb2014ye

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