Microfluidic Platform for Studying Chemotaxis of Adhesive Cells Revealed a Gradient-Dependent Migration and Acceleration of Cancer Stem Cells

Abstract

Recent studies reveal that solid tumors consist of heterogeneous cells with distinct phenotypes and functions. However, it is unclear how different subtypes of cancer cells migrate under chemotaxis. Here, we developed a microfluidic device capable of generating multiple stable gradients, culturing cells on-chip, and monitoring single cell migratory behavior. The microfluidic platform was used to study gradient-induced chemotaxis of lung cancer stem cell (LCSC) and differentiated LCSC (dLCSC) in real time. Our results showed the dynamic and differential response of both LCSC and dLCSC to chemotaxis, which was regulated by the β-catenin dependent Wnt signaling pathway. The microfluidic analysis showed that LCSC and dLCSC from the same origin behaved differently in the same external stimuli, suggesting the importance of cancer cell heterogeneity. We also observed for the first time the acceleration of both LCSC and dLCSC during chemotaxis caused by increasing local concentration in different gradients, which could only be realized through the microfluidic approach. The capability to analyze single cell chemotaxis under spatially controlled conditions provides a novel analytical platform for the study of cellular microenvironments and cancer cell metastasis.

Chemoresistant lung cancer stem cells display high DNA repair capability to remove cisplatin-induced DNA damage

“…They are known to express a list of biomarkers, such as CD15 and CD20 (Detail information: http://www.celprogen.com/details.php?pid=6423). This cell line was briefly characterized as described in a previous report (Zou et al, ). Third generation LCSCs (P3) were used in this study, and dLCSCs originated from LCSCs after 12 passages (P13) in the culture with an obvious change in cell morphology.…”

Microfluidic modelling of the tumor microenvironment for anti-cancer drug development

“…By observing cell behavior in these devices, it was found that different types of cancer cells may react differently to the same chemical stimuli. This dynamic response was regulated by the β-catenin dependent Wnt signaling pathway [202]. Most convection-based devices are gradient generators in which several specific chemical concentrations are generated by mixing the different amount of fluid.…”

PDMS-based microfluidic devices using commoditized PCBs as masters with no specialized equipment required

“…16,24 The relatively large scale in microstructure and the isotropic nature restrict PCB masters to be used in molding replicas with precise structures. However, the precision degree of PCB masters reaches the requirements of a lot of microuidic applications, such as cell-based assays, [28][29][30][31] droplet formation and operations, 22,32 microbead based analyses 33 and the generation of concentration gradients. 23 In this study, the insufficient adhesion due to the surface roughness was solved by sealing two semi-cured PDMS replicas.…”