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在入侵实验中,乳腺癌细胞核起引导作用。

In invasion assays, the breast cancer cell nucleus leads the way.

机构信息

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, 300 Pasteur Drive, H302, Stanford, CA, 94305, USA.

出版信息

BMC Res Notes. 2020 Oct 12;13(1):480. doi: 10.1186/s13104-020-05314-9.

DOI:10.1186/s13104-020-05314-9
PMID:33046121
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7552489/
Abstract

OBJECTIVE

Cancer cell metastasis determines disease prognosis. During cancer cell metastasis, the cancer cell and the cancer cell nucleus have to undergo extreme shape changes. To monitor shape changes of cancer cells and cancer cell nuclei and the positioning of the cancer cell nucleus during cancer cell invasion, a customized invasion assay with 8-μm pores and reconstituted basal membrane was imaged using fluorescence live-cell microscopy.

RESULTS

The observed cells changed their shape from a distinct fibroblast-like spindle shape to an amoeboid shape without polarization immediately after the passage through an 8-μm pore of the invasion assay. During the process of invasion, the cancer cell centered the cancer cell nucleus over the 8-μm pore, and cancer cell nucleus and adjacent cytoplasmic areas moved first through such a pore. Seemingly testing if the largest and least deformable organelle may fit, the cancer cell nucleus led the way through the porous membrane of the invasion assay.

摘要

目的

癌细胞转移决定着疾病的预后。在癌细胞转移过程中,癌细胞及其细胞核必须经历极端的形状变化。为了监测癌细胞和癌细胞核的形状变化以及癌细胞核在癌细胞侵袭过程中的定位,使用带有 8μm 孔的定制侵袭测定法和重建的基底膜,通过荧光活细胞显微镜进行成像。

结果

观察到的细胞在穿过侵袭测定法的 8μm 孔后,立即从明显的成纤维细胞样纺锤形变为非极化的阿米巴样形状。在侵袭过程中,癌细胞将癌细胞核定位于 8μm 孔的中心,然后癌细胞核和相邻的细胞质区域首先通过该孔移动。癌细胞核似乎在测试最大和最不易变形的细胞器是否可以通过,从而引领着穿过侵袭测定法的多孔膜。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d182/7552489/3a7766345694/13104_2020_5314_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d182/7552489/f779c93c49a0/13104_2020_5314_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d182/7552489/3a7766345694/13104_2020_5314_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d182/7552489/f779c93c49a0/13104_2020_5314_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d182/7552489/3a7766345694/13104_2020_5314_Fig2_HTML.jpg

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本文引用的文献

1
Molecular principles of metastasis: a hallmark of cancer revisited.转移的分子原理:重新审视癌症的一个标志
Signal Transduct Target Ther. 2020 Mar 12;5(1):28. doi: 10.1038/s41392-020-0134-x.
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Mechanisms of 3D cell migration.三维细胞迁移的机制。
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Nuclear positioning facilitates amoeboid migration along the path of least resistance.核定位有助于阿米巴样运动沿着最小阻力路径进行。
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Enucleated cells reveal differential roles of the nucleus in cell migration, polarity, and mechanotransduction.去核细胞揭示了细胞核在细胞迁移、极性和机械转导中的不同作用。
J Cell Biol. 2018 Mar 5;217(3):895-914. doi: 10.1083/jcb.201706097. Epub 2018 Jan 19.
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Amoeboid-mesenchymal migration plasticity promotes invasion only in complex heterogeneous microenvironments.阿米巴样-间充质迁移可塑性仅在复杂异质的微环境中促进侵袭。
Sci Rep. 2017 Aug 23;7(1):9237. doi: 10.1038/s41598-017-09300-3.
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Nuclear envelope rupture and repair during cancer cell migration.癌细胞迁移过程中的核膜破裂与修复
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ESCRT III repairs nuclear envelope ruptures during cell migration to limit DNA damage and cell death.ESCRT III 在细胞迁移过程中修复核膜破裂,以限制 DNA 损伤和细胞死亡。
Science. 2016 Apr 15;352(6283):359-62. doi: 10.1126/science.aad7611. Epub 2016 Mar 24.
9
Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival.核层粘连蛋白硬度是三维迁移的障碍,但柔软度可能会限制存活。
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Physical limits of cell migration: control by ECM space and nuclear deformation and tuning by proteolysis and traction force.细胞迁移的物理限制:细胞外基质空间和核变形的控制,以及蛋白水解和牵引力的调整。
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