Modeling of cancer metastasis and drug resistance via biomimetic nano-cilia and microfluidics
Journal
Biomaterials
Journal Volume
35
Journal Issue
5
Pages
1562-1571
Date Issued
2014
Author(s)
Kuo, C.-T.
Chiang, C.-L.
Chang, C.-H.
Liu, H.-K.
Huang, G.-S.
Lee, H.
Abstract
Three-dimensional (3D) tissue culture platforms that are capable of mimicking invivo 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 invitro and acquired enhanced metastatic propensity, as verified from microfluidic chemotaxis assay designed to replicate invivo-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. ? 2013 Elsevier Ltd.
SDGs
Other Subjects
Anti-cancer therapeutics; CSC; Drug resistance; EMT; Epithelial-mesenchymal transition; Metastasis; Multicellular spheroid; Physiological condition; Biochemistry; Biomimetics; Copolymers; Diseases; Pathology; Stem cells; Three dimensional; Tissue culture; Microfluidics; biomimetic material; breast cancer resistance protein; CD133 antigen; copolymer; Hermes antigen; hypoxia inducible factor 1alpha; nanocilium; nanomaterial; unclassified drug; article; cancer chemotherapy; cancer resistance; cancer stem cell; cell adhesion; cell assay; cell culture; cell line; chemotaxis; controlled study; cost effectiveness analysis; epithelial mesenchymal transition; eukaryotic flagellum; female; human; human cell; immunofluorescence; in vitro study; learning; metastasis; microfluidics; mucus secretion; multicellular spheroid; ovary cancer; phenotype; priority journal; three dimensional imaging; tissue culture; tumor microenvironment; upregulation; Biomimetic; CSC; Drug resistance; EMT; Metastasis; Microfluidics; Biomimetics; Cell Line, Tumor; Cilia; Drug Resistance, Neoplasm; Female; Fluorescent Antibody Technique; Humans; Microfluidics; Models, Biological; Nanostructures; Neoplasm Metastasis; Neoplasms
Type
journal article