Cell Rep:来看看清楚!癌细胞是如何扩散的

2017-07-07 中国生物技术网 中国生物技术网

日本东京大学的研究人员设计出一种新方法,从单细胞分辨率水平追踪癌细胞的转移模式。为了观看到组织内部,研究人员使小鼠全身和器官透明化,然后利用成像技术研究单个癌细胞转移到肺部、肠道和肝脏的过程。这种方法在癌症研究中将成为不可或缺的手段,尤其是在药物开发、治疗和诊断方面。

日本东京大学的研究人员设计出一种新方法,从单细胞分辨率水平追踪癌细胞的转移模式。为了观看到组织内部,研究人员使小鼠全身和器官透明化,然后利用成像技术研究单个癌细胞转移到肺部、肠道和肝脏的过程。这种方法在癌症研究中将成为不可或缺的手段,尤其是在药物开发、治疗和诊断方面。

肿瘤的转移总是从少数几个癌细胞的扩散开始,而这也是癌症治疗所面临的挑战。这些扩散的癌细胞隐藏在数以亿计的细胞背后,使得它们能够狡猾地逃脱研究人员的观察,医生和我们的免疫系统总是费力的去应付它们。现在,我们不用担心癌细胞的狡猾了。这项新研究方法以单细胞解析度去追踪癌细胞的扩散。该研究成果于7月5日发表在《Cell Reports》上。

东京大学的Hiroki Ueda教授和Kohei Miyazono教授开发了一种新方法生成小鼠的全身扫描图像。这项研究面临的挑战在于,利用使组织透明化的化学物质使小鼠身体变透明,而这种化学物质的配置必须刚刚合适。2014年,他们与RIKEN定量生物学中心合作,配置出了这种“化学鸡尾酒”——CUBIC(Clear Unobstructed Brain/Body Imaging Cocktail)。它可以让小鼠身体和重要器官透明化。但是当他们将CUBIC应用于癌症扩散追踪时,效果并不理想,因此他们进行了再次优化,又开发出了CUBIC-L和CUBIC-R这两个新版本。CUBIC-L和CUBIC-R的折光率非常好,折光率指光线通过时的弯曲程度,它显着地影响显微镜的成像方式。

CUBIC-L和CUBIC-R能够使小鼠身体透明化,同时不会影响癌细胞生成的荧光蛋白质的信号。这些荧光蛋白被用于追踪癌细胞扩散到多个器官中的过程,比如肝脏、胰腺、肠道等。下面这组图像展示了健康的肺部在两个星期的时间中被癌细胞逐渐侵入的过程。



这种在单细胞层面观察癌症的新方法提供了关于癌细胞转移的清晰视角,并且已经揭示出许多新见解。为了扩散到身体中,癌细胞必须进入到血液中,必须能够通过血管壁进或出。这对于癌细胞来说并不容易,很多癌细胞会死在这里,但是日本研究人员获得的图像表明,接受TGF-beta蛋白(调控细胞生长、分化)治疗的癌细胞更容易存活下来,也更容易形成恶性肿瘤。

Miyazono说:“在当前的研究中我们观察到了两种不同的脑转移瘤。第一种,扩散的癌细胞随着血管移动,这证实了血管是癌细胞转移的微环境。第二种,扩散的癌细胞离血管很远,表明血管对于大脑中形成的癌细胞群落并不是必须的。”

也许,这项研究最有意义的地方在于,使人们看到在被化疗破坏之后,这些陷入困境的癌细胞是如何生存的。通过对这些剩余的癌细胞仔细地研究,我们或许在未来可以找到治愈癌症更有效的方法。

Miyazono说:“在未来,对残余癌细胞的详细分析能够使我们更加理解癌症复发的机制,并给我们提供治疗癌症的线索。”

Ueda教授也说,这种身体透明化成像技术的升级版可以被用于人类临床诊断和治疗目的。他说:“我希望对人类样本的组织透明化和3D成像能够使病理诊断变得更容易、更客观、更精准。”

Ueda总结说:“在该研究中,我们展示了全身和重要器官透明化及单细胞解析度成像的效果。我们相信这种方法也适用于其他的生物化学研究,比如自体免疫和再生医学,单细胞解析度对于这些研究也非常重要。我们正在计划扩大全身组织透明化和成像方法的应用范围。”

原始出处:

Shimpei I. Kubota, Kei Takahashi, et al. Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution. Cell Reports. Volume 20, Issue 1, p236–250, 5 July 2017 

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    2017-09-29 维他命
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    2017-07-09 yxch36
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    2017-07-07 luominglian113

    学习了,谢谢分享

    0

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    2017-07-07 1e0f8808m18(暂无匿称)

    找到癌细胞转移规律并阻止,有望治愈癌症

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    2017-07-07 明月清辉

    谢谢分享,,学习了

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    2017-07-07 半夏微凉

    学习了谢谢分享

    0

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