Wang Zongjie, Xia Fan, Labib Mahmoud, Ahmadi Moloud, Chen Haijie, Das Jagotamoy, Ahmed Sharif U, Angers Stéphane, Sargent Edward H, Kelley Shana O
The Edward S. Rogers Sr. Department of Electrical & Computer Engineering, University of Toronto, Toronto, M5S 3G4, Canada.
Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, M5S 3G9, Canada.
ACS Nano. 2020 May 26;14(5):5324-5336. doi: 10.1021/acsnano.9b07350. Epub 2020 May 11.
Dynamic modulation of cellular phenotypes between the epithelial and mesenchymal states-the epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET)-plays an important role in cancer progression. Nanoscale topography of culture substrates is known to affect the migration and EMT of cancer cells. However, existing platforms heavily rely on simple geometries such as grooved lines or cylindrical post arrays, which may oversimplify the complex interaction between cells and nanotopography . Here, we use electrodeposition to construct finely controlled surfaces with biomimetic fractal nanostructures as a means of examining the roles of nanotopography during the EMT/MET process. We found that nanostructures in the size range of 100 to 500 nm significantly promote MET for invasive breast and prostate cancer cells. The "METed" cells acquired distinct expression of epithelial and mesenchymal markers, displayed perturbed morphologies, and exhibited diminished migration and invasion, even after the removal of a nanotopographical stimulus. The phosphorylation of GSK-3 was decreased, which further tuned the expression of Snail and modulated the EMT/MET process. Our findings suggest that invasive cancer cells respond to the geometries and dimensions of complex nanostructured architectures.
细胞表型在上皮状态和间充质状态之间的动态调节——上皮-间充质转化（EMT）和间充质-上皮转化（MET）——在癌症进展中起着重要作用。已知培养底物的纳米级形貌会影响癌细胞的迁移和EMT。然而，现有的平台严重依赖于简单的几何形状，如凹槽线或圆柱形柱阵列，这可能会过度简化细胞与纳米形貌之间的复杂相互作用。在这里，我们使用电沉积来构建具有仿生分形纳米结构的精细可控表面，作为研究纳米形貌在EMT/MET过程中作用的一种手段。我们发现，尺寸范围在100至500纳米的纳米结构显著促进侵袭性乳腺癌和前列腺癌细胞的MET。即使在去除纳米形貌刺激后，“METed”细胞也获得了上皮和间充质标志物的独特表达，呈现出紊乱的形态，并表现出迁移和侵袭能力的减弱。GSK-3的磷酸化减少，这进一步调节了Snail的表达并调控了EMT/MET过程。我们的研究结果表明，侵袭性癌细胞对复杂纳米结构的几何形状和尺寸有反应。
