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

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.

CD147 promotes proliferation and migration of oral cancer cells by inhibiting junctions between E‐cadherin and β‐catenin

“…Nevertheless, on the basis of these findings, we further explored the possible mechanisms underlying the effect of CD147 on the development and recurrence of OSCC, especially cervical lymph node metastasis. EMT was reported to be closely related to lymph node or distant metastasis in some malignant tumours, especially squamous cell carcinomas 6,28,29 . We found that E‐cadherin expression in the OSCC tissues was significantly lower than that in the adjacent oral mucosa.…”

“…Epithelial‐mesenchymal transition (EMT), a pathological process that polarizes epithelial cells to undergo various biological changes and obtain the phenotypes of mesenchymal cells, is considered to play an important role in invasion and metastasis during the progression of various cancers 5‐7 . Reduction of E‐cadherin is closely related to cancer cell EMT and leads to the loss of intercellular adhesion, destruction of the basement membrane morphology and subsequent decrease in the stability of the epithelium or vascular endothelium, thereby inducing metastasis 8‐10 .…”

Fluidity of Poly (ε-Caprolactone)-Based Material Induces Epithelial-to-Mesenchymal Transition

“…E-cadherin gene expression decreased and N-cadherin and vimentin expression was enhanced. This is the case when epithelial cells are cultured on a microfluidic device with a flow of healthy serum and heat-inactivated serum with C3a stimulate mesenchymal and epithelial phenotypes, respectively [40]. On the other hand, the viscosity of the normal breast epithelial cell was higher than that of cancer cells.…”

Mechanotactic Activation of TGF‐β by PEDOT Artificial Microenvironments Triggers Epithelial to Mesenchymal Transition

“…Nanotopographical cues can be utilized to understand the biophysical regulation of the cellular behavior . A plethora of nanotopographies such as nano‐dots, rods, wires, grooves, and pores have been engineered in the past to understand the regulation of cellular growth, function, adhesion, or differentiation. Studies have shown that precise control over cytoskeletal organization and cellular mobility can be achieved via 2D or 3D nanosurfaces .…”