A spatiotemporally defined in vitro microenvironment for controllable signal delivery and drug screening
Journal
Analyst
Journal Volume
139
Journal Issue
19
Pages
4846-4854
Date Issued
2014
Author(s)
Kuo, C.-T.
Liu, H.-K.
Huang, G.-S.
Chang, C.-H.
Chen, C.-L.
Chen, K.-C.
Lee, H.
Abstract
Cancer metastasis and drug resistance are important malignant tumor phenotypes that cause roughly 90% mortality in human cancers. Current therapeutic strategies, however, face substantial challenges partially due to a lack of applicable pre-clinical models and drug-screening platforms. Notably, microscale and three-dimensional (3D) tissue culture platforms capable of mimicking in vivo microenvironments to replicate physiological conditions have become vital tools in a wide range of cellular and clinical studies. Here, we present a microfluidic device capable of mimicking a configurable tumor microenvironment to study in vivo-like cancer cell migration as well as screening of inhibitors on both parental tumors and migratory cells. In addition, a novel evaporation-based paper pump was demonstrated to achieve adaptable and sustainable concentration gradients for up to 6 days in this model. This straightforward modeling approach allows for fast patterning of a wide variety of cell types in 3D and may be further integrated into biological assays. We also demonstrated cell migration from tumor spheroids induced by an epidermal growth factor (EGF) gradient and exhibited lowered expression of an epithelial marker (EpCAM) compared with parental cells, indicative of partial epithelial-mesenchymal transition (EMT) in this process. Importantly, pseudopodia protrusions from the migratory cells – critical during cancer metastasis – were demonstrated. Insights gained from this work offer new opportunities to achieve active control of in vitro tumor microenvironments on-demand, and may be amenable towards tailored clinical applications. ? 2014 the Partner Organisations.
SDGs
Other Subjects
cell adhesion molecule; epidermal growth factor; messenger RNA; paclitaxel; tumor antigen; tumor-associated antigen GA733; biological model; cell motion; culture technique; cytology; devices; drug effects; drug screening; epithelial mesenchymal transition; human; MCF 7 cell line; metabolism; microfluidic analysis; multicellular spheroid; procedures; tumor cell line; tumor microenvironment; Antigens, Neoplasm; Cell Adhesion Molecules; Cell Culture Techniques; Cell Line, Tumor; Cell Movement; Drug Evaluation, Preclinical; Epidermal Growth Factor; Epithelial-Mesenchymal Transition; Humans; MCF-7 Cells; Microfluidic Analytical Techniques; Models, Biological; Paclitaxel; RNA, Messenger; Spheroids, Cellular; Tumor Microenvironment
Type
journal article