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Bioengineering 2018, 5(2), 40; https://doi.org/10.3390/bioengineering5020040

A Microfluidic System for the Investigation of Tumor Cell Extravasation

1
Department of Mechanical und Medical Engineering, Hochschule Furtwangen University, Villingen-Schwenningen 78054, Germany
2
Department of Biochemical Engineering, University College London, London WC1E 6BT, UK
3
Hahn-Schickard, Villingen-Schwenningen 78054, Germany, sabrina_daluz@yahoo.de
4
HFU Hochschule Furtwangen, Department Medical and Life Science, Villingen-Schwenningen 78054, Germany
*
Authors to whom correspondence should be addressed.
Received: 16 March 2018 / Revised: 17 May 2018 / Accepted: 21 May 2018 / Published: 23 May 2018
(This article belongs to the Special Issue Advances in Micro-Bioreactor Design for Organ Cell Studies)
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Abstract

Metastatic dissemination of cancer cells is a very complex process. It includes the intravasation of cells into the metastatic pathways, their passive distribution within the blood or lymph flow, and their extravasation into the surrounding tissue. Crucial steps during extravasation are the adhesion of the tumor cells to the endothelium and their transendothelial migration. However, the molecular mechanisms that are underlying this process are still not fully understood. Novel three dimensional (3D) models for research on the metastatic cascade include the use of microfluidic devices. Different from two dimensional (2D) models, these devices take cell–cell, structural, and mechanical interactions into account. Here we introduce a new microfluidic device in order to study tumor extravasation. The device consists of three different parts, containing two microfluidic channels and a porous membrane sandwiched in between them. A smaller channel together with the membrane represents the vessel equivalent and is seeded separately with primary endothelial cells (EC) that are isolated from the lung artery. The second channel acts as reservoir to collect the migrated tumor cells. In contrast to many other systems, this device does not need an additional coating to allow EC growth, as the primary EC that is used produces their own basement membrane. VE-Cadherin, an endothelial adherence junction protein, was expressed in regular localization, which indicates a tight barrier function and cell–cell connections of the endothelium. The EC in the device showed in vivo-like behavior under flow conditions. The GFP-transfected tumor cells that were introduced were of epithelial or mesenchymal origin and could be observed by live cell imaging, which indicates tightly adherent tumor cells to the endothelial lining under different flow conditions. These results suggest that the new device can be used for research on molecular requirements, conditions, and mechanism of extravasation and its inhibition. View Full-Text
Keywords: microfluidic device; HPAEC; tumor cell extravasation microfluidic device; HPAEC; tumor cell extravasation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Kühlbach, C.; da Luz, S.; Baganz, F.; Hass, V.C.; Mueller, M.M. A Microfluidic System for the Investigation of Tumor Cell Extravasation. Bioengineering 2018, 5, 40.

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