Sci Adv:癌细胞为了转移长出“手指”!高侵袭性肺癌前导细胞“手指”更长

2020-07-31 Cathy 转化医学网

肿瘤的异质性是恶性肿瘤的特征之一,是指肿瘤在生长过程中,经过多次分裂增殖,其子细胞呈现出分子生物学或基因方面的改变,从而使肿瘤的生长速度、侵袭能力、对药物的敏感性、预后等各方面产生差异。

肿瘤的异质性是恶性肿瘤的特征之一,是指肿瘤在生长过程中,经过多次分裂增殖,其子细胞呈现出分子生物学或基因方面的改变,从而使肿瘤的生长速度、侵袭能力、对药物的敏感性、预后等各方面产生差异。同一肿瘤中可以存在有很多不同的基因型或者亚型的细胞。

在侵袭性肿瘤中,存在“前导细胞”和“跟随细胞”,这两种细胞亚群在肿瘤转移过程中相互协作。近期,有研究团队发现,一种叫做丝状伪足的微小“手指”状突起会驱动肺癌细胞的侵袭行为,且前导细胞比跟随细胞具有更长的“手指”。依据这一发现,他们开发出了一种创新技术,能分离前导细胞和跟随细胞。这对实现肿瘤的精准治疗具有十分重要的意义。

该研究由埃默里大学的血液学和肿瘤医学教授Adam Marcus领导,并于2020年7月24日发表在《科学进展》上,题目为“Epigenetically heterogeneous tumor cells direct collective invasion through filopodia-driven fibronectin micropatterning”

这项发现有助于研究人员通过了解肿瘤内致命转移所必需的稀有细胞,开发出防止癌症扩散的治疗方法。Marcus表示,区分前导细胞和侵袭行为的持久表观遗传变化可能出现在几种类型的癌症中。

Marcus先前的研究表明了,前导细胞和更常见的对应细胞(跟随细胞)是如何共同组成一个侵袭性细胞群的。这两种肿瘤细胞的迁移率和存活率相互依赖,但具有不同的基因活性模式,甚至具有不同的形状。

特别是,前导细胞比跟随细胞显示出更长的丝状伪足。

研究人员说:“丝状伪足就像细胞的手指一样,可以帮助细胞前进。”

他们还发现,丝状伪足较长与一种叫做MYO10的基因有关,该基因编码稳定丝状伪足的内部细胞骨架的一种成分。与跟随细胞相比,MYO10是前导细胞中表达上调和甲基化程度最高的基因,而长丝状伪足和侵袭行为都依赖于MYO10的活性。

Marcus说:“众所周知,MYO10与侵袭和转移有关,但这是第一个证据表明它在一个罕见的细胞亚群中发挥着这种特殊作用。这有助于我们在患者肿瘤中寻找这些罕见的细胞,以判断它们的潜在侵袭性。”

前导细胞也分泌纤维结合蛋白,一种粘性的细胞外蛋白,而跟随细胞则不分泌。MYO10蛋白有助于丝状伪足将纤维结合蛋白分子重新排列成纤维,但它似乎并不直接与纤维结合蛋白相互作用。

研究人员表示:“当前导细胞丝状伪足拉动细胞外基质时,它们会将这种基质从一个随机的网状结构变为细胞前方的长而平行的轨道,为细胞群的运动铺平了道路。”

丝状伪足有时被描述为类似触角或更稳定的细胞结构的前体。

Marcus说:“我们观察到,在前导细胞中,丝状伪足不仅是细胞外环境的传感器,而且还积极参与了细胞外基质的重组 。”

研究人员还探究了识别前导细胞的其他变化,例如Jagged1基因表达的上调。Jagged1编码Notch通路的一个受体,其活性依赖于MYO10的激活。MYO10和Jagged/Notch激活或许可以推广到患者样本和其他类型的癌症。

原始出处:Emily R. Summerbe,Janna K. Mouw, Joshua S. K. Bell, et al. Epigenetically heterogeneous tumor cells direct collective invasion through filopodia-driven fibronectin micropatterning. Science Advances 24 Jul 2020

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    2020-08-07 yangchou

    学习了,谢谢

    0

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    2020-08-02 yxch36
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    2020-08-02 sunyl07
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    2020-08-01 ms3000000449926787

    学习了

    0

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    2020-08-01 619103330

    不错

    0

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