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Biomaterials. 2014 Feb;35(5):1562-71. doi: 10.1016/j.biomaterials.2013.11.008. Epub 2013 Nov 22.

Modeling of cancer metastasis and drug resistance via biomimetic nano-cilia and microfluidics.

Author information

1
Institute of Applied Mechanics, National Taiwan University, Taipei, Taiwan, ROC.
2
School of Biomedical Science, Ohio State University, Columbus, USA.
3
Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
4
Department of Obstetrics & Gynaecology, National University Hospital, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore.
5
Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC. Electronic address: hsinyu@ntu.edu.tw.
6
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC. Electronic address: huangcs@ntu.edu.tw.
7
Institute of Applied Mechanics, National Taiwan University, Taipei, Taiwan, ROC. Electronic address: andrew@iam.ntu.edu.tw.

Abstract

Three-dimensional (3D) tissue culture platforms that are capable of mimicking in vivo microenvironments to replicate physiological conditions are vital tools in a wide range of cellular and clinical studies. Here, learning from the nature of cilia in lungs - clearing mucus and pathogens from the airway - we develop a 3D culture approach via flexible and kinetic copolymer-based chains (nano-cilia) for diminishing cell-to-substrate adhesion. Multicellular spheroids or colonies were tested for 3-7 days in a microenvironment consisting of generated cells with properties of putative cancer stem cells (CSCs). The dynamic and reversible regulation of epithelial-mesenchymal transition (EMT) was examined in spheroids passaged and cultured in copolymer-coated dishes. The expression of CSC markers, including CD44, CD133, and ABCG2, and hypoxia signature, HIF-1α, was significantly upregulated compared to that without the nano-cilia. In addition, these spheroids exhibited chemotherapeutic resistance in vitro and acquired enhanced metastatic propensity, as verified from microfluidic chemotaxis assay designed to replicate in vivo-like metastasis. The biomimetic nano-cilia approach and microfluidic device may offer new opportunities to establish a rapid and cost-effective platform for the study of anti-cancer therapeutics and CSCs.

KEYWORDS:

Biomimetic; CSC; Drug resistance; EMT; Metastasis; Microfluidics

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