Nanochip-Induced Epithelial-to-Mesenchymal Transition: Impact of Physical Microenvironment on Cancer Metastasis

Udesh Dhawan, Ming Wen Sue, Kuan Chun Lan, Waradee Buddhakosai, Pao Hui Huang, Yi Cheng Chen, Po Chun Chen*, Wen-Liang Chen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Epithelial-to-mesenchymal transition (EMT) is a highly orchestrated process motivated by the nature of physical and chemical compositions of the tumor microenvironment (TME). The role of the physical framework of the TME in guiding cells toward EMT is poorly understood. To investigate this, breast cancer MDA-MB-231 and MCF-7 cells were cultured on nanochips comprising tantalum oxide nanodots ranging in diameter from 10 to 200 nm, fabricated through electrochemical approach and collectively referred to as artificial microenvironments. The 100 and 200 nm nanochips induced the cells to adopt an elongated or spindle-shaped morphology. The key EMT genes, E-cadherin, N-cadherin, and vimentin, displayed the spatial control exhibited by the artificial microenvironments. The E-cadherin gene expression was attenuated, whereas those of N-cadherin and vimentin were amplified by 100 and 200 nm nanochips, indicating the induction of EMT. Transcription factors, snail and twist, were identified for modulating the EMT genes in the cells on these artificial microenvironments. Localization of EMT proteins observed through immunostaining indicated the loss of cell-cell junctions on 100 and 200 nm nanochips, confirming the EMT induction. Thus, by utilizing an in vitro approach, we demonstrate how the physical framework of the TME may possibly trigger or assist in inducing EMT in vivo. Applications in the fields of drug discovery, biomedical engineering, and cancer research are expected.

Original languageEnglish
Pages (from-to)11474-11485
Number of pages12
JournalACS Applied Materials and Interfaces
Volume10
Issue number14
DOIs
StatePublished - 11 Apr 2018

Keywords

  • artificial microenvironments
  • epithelial to mesenchymal transition
  • nanodots
  • nanotopography
  • tantalum oxide
  • triple negative breast cancer

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