Abstract：
Epithelial-mesenchymal transition (EMT) is critical for tumor invasion and many other cell-relevant processes. While much progress has been made about EMT, no report concerns the EMT of cells on topological biomaterial interfaces with significant nuclear deformation. Herein, we prepared a poly(lactide-co-glycolide) micropillar array with an appropriate dimension to enable significant deformation of cell nuclei and examined EMT of a human lung cancer epithelial cell (A549). We show that A549 cells undergo serious nuclear deformation on the micropillar array. The cells express more E-cadherin and less vimentin on the micropillar array than on the smooth surface. After transforming growth factor-β1 (TGF-β1) treatment, the expression of E-cadherin as an indicator of the epithelial phenotype is decreased and the expression of vimentin as an indicator of the mesenchymal phenotype is increased for the cells both on smooth surfaces and on micropillar arrays, indicating that EMT occurs even when the cell nuclei are deformed and the culture on the micropillar array more enhances the expression of vimentin. Expression of myosin phosphatase targeting subunit 1 is reduced in the cells on the micropillar array, possibly affecting the turnover of myosin light chain phosphorylation and actin assembly; this makes cells on the micropillar array prefer the epithelial-like phenotype and more sensitive to TGF-β1. Overall, the micropillar array exhibits a promoting effect on the EMT.
摘要：
上皮-间质转化（EMT）对于肿瘤侵袭和许多其他细胞相关过程至关重要。虽然EMT取得了很大进展，没有报告涉及具有明显核变形的拓扑生物材料界面上细胞的EMT。在这里，我们制备了具有适当尺寸的聚(丙交酯-共-乙交酯)微柱阵列,以使得细胞核能够显著变形,并检查了人肺癌上皮细胞(A549)的EMT。我们显示A549细胞在微柱阵列上发生严重的核变形。细胞在微柱阵列上比在光滑表面上表达更多的E-钙粘蛋白和更少的波形蛋白。转化生长因子-β1（TGF-β1）治疗后，对于光滑表面和微柱阵列上的细胞，E-cadherin作为上皮表型指标的表达减少，波形蛋白作为间充质表型指标的表达增加，表明即使细胞核变形也会发生EMT，并且微柱阵列上的培养物更加增强波形蛋白的表达。肌球蛋白磷酸酶靶向亚基1的表达在微柱阵列上的细胞中减少，可能影响肌球蛋白轻链磷酸化和肌动蛋白组装的周转；这使得微柱阵列上的细胞更喜欢上皮样表型，对TGF-β1更敏感。总的来说,微柱阵列对EMT表现出促进作用。
