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Microfluidic Tumor-on-a-Chip Model to Study Tumor Metabolic Vulnerability
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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730115/ https://www.ncbi.nlm.nih.gov/pubmed/33260673 http://dx.doi.org/10.3390/ijms21239075 |
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author | Ayuso, Jose M Rehman, Shujah Farooqui, Mehtab Virumbrales-Muñoz, María Setaluri, Vijayasaradhi Skala, Melissa C Beebe, David J |
author_facet | Ayuso, Jose M Rehman, Shujah Farooqui, Mehtab Virumbrales-Muñoz, María Setaluri, Vijayasaradhi Skala, Melissa C Beebe, David J |
author_sort | Ayuso, Jose M |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7730115 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77301152020-12-12 Microfluidic Tumor-on-a-Chip Model to Study Tumor Metabolic Vulnerability Ayuso, Jose M Rehman, Shujah Farooqui, Mehtab Virumbrales-Muñoz, María Setaluri, Vijayasaradhi Skala, Melissa C Beebe, David J Int J Mol Sci Article 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. MDPI 2020-11-28 /pmc/articles/PMC7730115/ /pubmed/33260673 http://dx.doi.org/10.3390/ijms21239075 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ayuso, Jose M Rehman, Shujah Farooqui, Mehtab Virumbrales-Muñoz, María Setaluri, Vijayasaradhi Skala, Melissa C Beebe, David J Microfluidic Tumor-on-a-Chip Model to Study Tumor Metabolic Vulnerability |
title | Microfluidic Tumor-on-a-Chip Model to Study Tumor Metabolic Vulnerability |
title_full | Microfluidic Tumor-on-a-Chip Model to Study Tumor Metabolic Vulnerability |
title_fullStr | Microfluidic Tumor-on-a-Chip Model to Study Tumor Metabolic Vulnerability |
title_full_unstemmed | Microfluidic Tumor-on-a-Chip Model to Study Tumor Metabolic Vulnerability |
title_short | Microfluidic Tumor-on-a-Chip Model to Study Tumor Metabolic Vulnerability |
title_sort | microfluidic tumor-on-a-chip model to study tumor metabolic vulnerability |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730115/ https://www.ncbi.nlm.nih.gov/pubmed/33260673 http://dx.doi.org/10.3390/ijms21239075 |
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