Metabolic Switching of Tumor Cells under Hypoxic Conditions in a Tumor-on-a-chip Model

Department of Biochemistry, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands

Applied Microfluidics for BioEngineering Research, TechMed Center & MESA+ Institute for Nanotechnology, University of Twente, Postbus 217, 7500AE Enschede, The Netherlands

Authors to whom correspondence should be addressed.

^†

These authors have equally contributed to this work.

Micromachines 2020, 11(4), 382; https://doi.org/10.3390/mi11040382

Received: 14 March 2020 / Revised: 31 March 2020 / Accepted: 2 April 2020 / Published: 4 April 2020

(This article belongs to the Special Issue 10th Anniversary of Micromachines)

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Abstract

Hypoxia switches the metabolism of tumor cells and induces drug resistance. Currently, no therapeutic exists that effectively and specifically targets hypoxic cells in tumors. Development of such therapeutics critically depends on the availability of in vitro models that accurately recapitulate hypoxia as found in the tumor microenvironment. Here, we report on the design and validation of an easy-to-fabricate tumor-on-a-chip microfluidic platform that robustly emulates the hypoxic tumor microenvironment. The tumor-on-a-chip model consists of a central chamber for 3D tumor cell culture and two side channels for medium perfusion. The microfluidic device is fabricated from polydimethylsiloxane (PDMS), and oxygen diffusion in the device is blocked by an embedded sheet of polymethyl methacrylate (PMMA). Hypoxia was confirmed using oxygen-sensitive probes and the effect on the 3D tumor cell culture investigated by a pH-sensitive dual-labeled fluorescent dextran and a fluorescently labeled glucose analogue. In contrast to control devices without PMMA, PMMA-containing devices gave rise to decreases in oxygen and pH levels as well as an increased consumption of glucose after two days of culture, indicating a rapid metabolic switch of the tumor cells under hypoxic conditions towards increased glycolysis. This platform will open new avenues for testing anti-cancer therapies targeting hypoxic areas. View Full-Text

Keywords: Tumor-on-a-chip; Hypoxia; pH; Microfluidics; PDMS; Cell metabolism

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MDPI and ACS Style

Palacio-Castañeda, V.; Kooijman, L.; Venzac, B.; Verdurmen, W.P.R.; Le Gac, S. Metabolic Switching of Tumor Cells under Hypoxic Conditions in a Tumor-on-a-chip Model. Micromachines 2020, 11, 382. https://doi.org/10.3390/mi11040382

AMA Style

Palacio-Castañeda V, Kooijman L, Venzac B, Verdurmen WPR, Le Gac S. Metabolic Switching of Tumor Cells under Hypoxic Conditions in a Tumor-on-a-chip Model. Micromachines. 2020; 11(4):382. https://doi.org/10.3390/mi11040382

Chicago/Turabian Style

Palacio-Castañeda, Valentina, Lucas Kooijman, Bastien Venzac, Wouter P.R. Verdurmen, and Séverine Le Gac. 2020. "Metabolic Switching of Tumor Cells under Hypoxic Conditions in a Tumor-on-a-chip Model" Micromachines 11, no. 4: 382. https://doi.org/10.3390/mi11040382

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Metabolic Switching of Tumor Cells under Hypoxic Conditions in a Tumor-on-a-chip Model

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