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生物界面各向异性调节乳腺癌细胞的迁移。

Biointerface anisotropy modulates migration of breast cancer cell.

机构信息

School of Physical Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai, 201210, China; Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Changning, Shanghai, 200050, China; University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan, Beijing, 100049, China.

School of Physical Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai, 201210, China; Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.

出版信息

Colloids Surf B Biointerfaces. 2020 Jun;190:110973. doi: 10.1016/j.colsurfb.2020.110973. Epub 2020 Mar 13.

Abstract

Migration of cancer cell is a cyclic process, which involves dynamic interaction between extracellular biointerface and cellular responds. In tumors, collagen as extracellular matrix reorganizes biointerface from curl and isotropic fibers to straightened and anisotropic fibers during tumorigenesis, yet how cell migration respond to topography of biointerface is unknown. In this research, we introduced a facile fabrication method on nanofibers of varying topography, which was mimicking the alignment of extracellular nanofibers, to examine the change of cytoskeleton during cell migration. We took advantage of breast carcinoma cell line (MDA-MB-231) for time-lapse imaging analysis. We found that biointerface anisotropy modulated morphology of cell and mediated the pattern of migration. Morphologically, cells on anisotropic nanofiber showed extending spindle shape. The trajectories of migration templated the topographic pattern on biointerface. Besides, aligned nanofiber induced caterpillar-like model of migration through protrusion - retraction cycle, which was indicated by periodical variation of aspect ratio and velocity of cells. The biointerface anisotropy triggered vimentin filaments and microtubule networks preferentially oriented along the alignment of nanofibers. And the velocity of cell mobility by vimentin, β-catenin or CDC42 knockdown was significantly enhanced on aligned nanofibers. Thus, we implied that biointerface anisotropy modulated migration of breast cancer cell and it associated with reorganization of cytoskeleton filaments.

摘要

癌细胞的迁移是一个循环过程,涉及细胞外生物界面和细胞反应之间的动态相互作用。在肿瘤中,胶原蛋白作为细胞外基质,在肿瘤发生过程中使生物界面从卷曲和各向同性纤维重新组织为拉直和各向异性纤维,然而细胞迁移如何响应生物界面的形貌尚不清楚。在这项研究中,我们介绍了一种简便的制造方法,可以在纳米纤维上制造出不同形貌的纳米纤维,模仿细胞外纳米纤维的排列,以研究细胞迁移过程中细胞骨架的变化。我们利用乳腺癌细胞系(MDA-MB-231)进行延时成像分析。我们发现,生物界面各向异性调节了细胞的形态,并介导了迁移的模式。形态上,在各向异性纳米纤维上的细胞表现出延伸的纺锤形。迁移的轨迹模仿了生物界面的形貌模式。此外,排列的纳米纤维通过突起-回缩循环诱导类似毛毛虫的迁移模式,这表现为细胞纵横比和速度的周期性变化。生物界面的各向异性触发波形蛋白丝和微管网络优先沿着纳米纤维的排列方向取向。并且,通过波形蛋白、β-连环蛋白或 CDC42 敲低,细胞迁移的速度在排列的纳米纤维上显著提高。因此,我们推测生物界面各向异性调节了乳腺癌细胞的迁移,并且与细胞骨架丝的重组有关。

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