Nanostructured Architectures Promote the Mesenchymal-Epithelial Transition for Invasive Cells

Zongjie Wang; Fan Xia; Mahmoud Labib; Moloud Ahmadi; Haijie Chen; Jagotamoy Das; Sharif U. Ahmed; Stéphane Angers; Edward H. Sargent; Shana O. Kelley

doi:10.1021/acsnano.9b07350

Nanostructured Architectures Promote the Mesenchymal-Epithelial Transition for Invasive Cells

Zongjie Wang, Fan Xia, Mahmoud Labib, Moloud Ahmadi, Haijie Chen, Jagotamoy Das, Sharif U. Ahmed, Stéphane Angers, Edward H. Sargent, Shana O. Kelley^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

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 in vivo. 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.

Original language	English (US)
Pages (from-to)	5324-5336
Number of pages	13
Journal	ACS nano
Volume	14
Issue number	5
DOIs	https://doi.org/10.1021/acsnano.9b07350
State	Published - May 26 2020

Funding

This research was supported in part by the Canadian Institutes of Health Research (grant no. FDN-148415) and the Natural Sciences and Engineering Research Council of Canada (grant no. RGPIN-2016-06090). This research is part of the University of Toronto's Medicine by Design initiative, which receives funding from the Canada First Research Excellence Fund. Z.W. was supported by an Alexander Graham Bell Canada Graduate Scholarship. This research was supported in part by the Canadian Institutes of Health Research (grant no. FDN-148415) and the Natural Sciences and Engineering Research Council of Canada (grant no. RGPIN-2016-06090). This research is part of the University of Toronto\u2019s Medicine by Design initiative, which receives funding from the Canada First Research Excellence Fund. Z.W. was supported by an Alexander Graham Bell Canada Graduate Scholarship.

Keywords

cancer biology
electrodeposition
epithelial-mesenchymal transition
mechanobiology
nanostructured microarchitectures

ASJC Scopus subject areas

General Materials Science
General Engineering
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acsnano.9b07350

Cite this

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abstract = "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 in vivo. 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.",

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AU - Das, Jagotamoy

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Nanostructured Architectures Promote the Mesenchymal-Epithelial Transition for Invasive Cells

Abstract

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Keywords

ASJC Scopus subject areas

UN SDGs

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