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Microfluidic Tumor-on-a-Chip Model to Study Tumor Metabolic Vulnerability

Authors :
Mehtab Farooqui
Melissa C. Skala
María Virumbrales-Muñoz
Jose M. Ayuso
Vijayasaradhi Setaluri
Shujah Rehman
David J. Beebe
Source :
International Journal of Molecular Sciences, Vol 21, Iss 9075, p 9075 (2020), International Journal of Molecular Sciences, Volume 21, Issue 23
Publication Year :
2020
Publisher :
MDPI AG, 2020.

Abstract

Tumor-specific metabolic adaptations offer an interesting therapeutic opportunity to selectively destroy cancer cells. However, solid tumors also present gradients of nutrients and waste products across the tumor mass, forcing tumor cells to adapt their metabolism depending on nutrient availability in the surrounding microenvironment. Thus, solid tumors display a heterogenous metabolic phenotype across the tumor mass, which complicates the design of effective therapies that target all the tumor populations present. In this work, we used a microfluidic device to study tumor metabolic vulnerability to several metabolic inhibitors. The microdevice included a central chamber to culture tumor cells in a three-dimensional (3D) matrix, and a lumen in one of the chamber flanks. This design created an asymmetric nutrient distribution across the central chamber, generating gradients of cell viability. The results revealed that tumor cells located in a nutrient-enriched environment showed low to no sensitivity to metabolic inhibitors targeting glycolysis, fatty acid oxidation, or oxidative phosphorylation. Conversely, when cell density inside of the model was increased, compromising nutrient supply, the addition of these metabolic inhibitors disrupted cellular redox balance and led to tumor cell death.

Details

Language :
English
ISSN :
16616596 and 14220067
Volume :
21
Issue :
9075
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences
Accession number :
edsair.doi.dedup.....0377838d07182ad84c57fd0f3dd3043a