通过粘着斑的形态变化激活细胞迁移依赖于 MYCN 扩增神经母细胞瘤细胞中的剪切力。
Activation of cell migration via morphological changes in focal adhesions depends on shear stress in MYCN-amplified neuroblastoma cells.
机构信息
1 Department of Biosciences and Informatics, Keio University , Kanagawa , Japan.
2 Department of Mechanical Engineering, Keio University , Kanagawa , Japan.
出版信息
J R Soc Interface. 2019 Mar 29;16(152):20180934. doi: 10.1098/rsif.2018.0934.
Neuroblastoma is the most common solid tumour of childhood, and it metastasizes to distant organs. However, the mechanism of metastasis, which generally depends on the cell motility of the neuroblastoma, remains unclear. In many solid tumours, it has been reported that shear stress promotes metastasis. Here, we investigated the relationship between shear stress and cell motility in the MYCN-amplified human neuroblastoma cell line IMR32, using a microfluidic device. We confirmed that most of the cells migrated downstream, and cell motility increased dramatically when the cells were exposed to a shear stress of 0.4 Pa, equivalent to that expected in vivo. We observed that the morphological features of focal adhesion were changed under a shear stress of 0.4 Pa. We also investigated the relationship between malignancy and the motility of IMR32 cells under shear stress. Decreasing the expression of MYCN in IMR32 cells via siRNA transfection inhibited cell motility by a shear stress of 0.4 Pa. These results suggest that MYCN-amplified neuroblastoma cells under high shear stress migrate to distant organs due to high cell motility, allowing cell migration to lymphatic vessels and venules.
神经母细胞瘤是儿童最常见的实体肿瘤，它会转移到远处的器官。然而，转移的机制，通常取决于神经母细胞瘤的细胞迁移能力，目前仍不清楚。在许多实体肿瘤中，已经有报道表明切应力促进转移。在这里，我们使用微流控装置研究了 MYCN 扩增的人神经母细胞瘤细胞系 IMR32 中的切应力与细胞迁移之间的关系。我们证实，大多数细胞向下游迁移，当细胞暴露于 0.4Pa 的切应力时，细胞迁移能力显著增加，这相当于体内的预期值。我们观察到在 0.4Pa 的切应力下，焦点黏附的形态特征发生了变化。我们还研究了 IMR32 细胞在切应力下的恶性程度与迁移能力之间的关系。通过 siRNA 转染降低 IMR32 细胞中 MYCN 的表达，通过 0.4Pa 的切应力抑制了细胞迁移。这些结果表明，高切应力下的 MYCN 扩增神经母细胞瘤细胞由于高细胞迁移能力而迁移到远处的器官，允许细胞迁移到淋巴管和小静脉。
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