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Nat Commun:研究人员发现促进癌细胞转移的特殊肿瘤环境

2017-11-22 sunshine2015译自 medicalxpress 来宝网

加利福尼亚大学圣地亚哥分校的生物工程师和生物信息学家发现了肿瘤周围的环境如何引发癌细胞的转移行为。具体而言,当肿瘤细胞聚集在密集的环境中时,研究人员发现他们开启了一组特定的基因,并开始形成类似于血管的结构。

加利福尼亚大学圣地亚哥分校的生物工程师和生物信息学家发现了肿瘤周围的环境如何引发癌细胞的转移行为。具体而言,当肿瘤细胞聚集在密集的环境中时,研究人员发现他们开启了一组特定的基因,并开始形成类似于血管的结构。

过去,医生在临床中观察到这些血管样结构,这种现象称为血管模仿,与一些最具侵袭性的癌症有关。但他们不明白是什么导致了这个转变。

这项研究增加了研究人员如何启动转移过程的知识。加州大学圣地亚哥分校生物工程教授,研究负责人Stephanie Fraley说:“我们擅长瞄准肿瘤生长,但对转移的了解还不够。”

肿瘤细胞从一个位置转移到另一个位置是导致90%的癌症相关死亡的原因。研究人员发现的一组称为基因模块的基因能够预测患者的预期寿命,以及肿瘤是否会在包括乳腺癌肺癌胰腺癌和肾癌在内的9种癌症中转移。

该基因模块可用于帮助确定患者是否患有侵袭性癌症,并通知患者和他们的医生在选择特定疗法时作出的决定。

研究人员在11月21日的“自然通讯”杂志上详细介绍了他们的发现。

研究人员能够通过将恶性细胞置于他们建立的定制3D胶原基质中进行观察。他们发现细胞在由短纤维和小孔(与长纤维和大孔相对)构成的基质包围时变成模拟血管的结构,并且这种现象与基质的其他物理特征如硬度相似。这一发现令人惊讶。

该研究的第一作者,博士生Daniel Ortiz Velez说:“我们认为把细胞放入这个更加有限的环境将会阻止它们的传播。 Fraley实验室的学生。 “但是恰恰相反。”

研究人员说,细胞在传统的培养皿中没有表现出这种行为。

Fraley说:“将细胞包围在模拟人体内发生的3D环境中是至关重要的。

进一步钻研,研究人员发现细胞的行为是由特定的基因模块引起的,他们将胶原诱导的网络表型称为CINP。把这些细胞放入一个受限制的环境,基本上重写了它们的基因表达。 “这几乎就像矩阵编码基因模块一样,”Fraley说。

另外,研究人员在一系列人类癌症基因表达和组织学数据库中寻找这个基因模块,其中包含组织的微观结构的记录。该模块的存在是控制其他因素(如患者年龄)后是否可能积极转移癌症的强有力预测指标。

这是有道理的,因为由恶性细胞建立的通道允许血液流动到肿瘤而不凝固并有助于营养物质。研究人员推测,这也使癌细胞更容易通过患者的血液传播。其他研究表明,当癌细胞连接起来时,它提高了它们传播到体内远处的机会。

接下来的步骤包括在动物研究和其他人类数据集中测试该方法。研究人员也将寻找分子靶点来阻止细胞的转化。

研究人员正在谈判授权他们的方法。

原始出处:D. O. Velez, B. Tsui, T. Goshia, et al. 3D collagen architecture induces a conserved migratory and transcriptional response linked to vasculogenic mimicry. Nat Commun(2017).

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    2018-10-30 liuli5079
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    2018-10-21 一叶知秋
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    2017-11-24 飘飘爱

    很好

    0

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    2017-11-24 yxch36
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    2017-11-24 zz72
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    2017-11-22 Y—xianghai

    学习了新知识

    0

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