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Microfluidic Tumor-on-a-Chip Model to Study Tumor Metabolic Vulnerability
- 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.
- Subjects :
- tumor-on-a-chip
microfluidics
Cell Count
Oxidative phosphorylation
Matrix (biology)
Models, Biological
Catalysis
Article
Inorganic Chemistry
lcsh:Chemistry
Necrosis
Lab-On-A-Chip Devices
Neoplasms
Humans
Glycolysis
Viability assay
Physical and Theoretical Chemistry
redox ratio
Molecular Biology
Beta oxidation
lcsh:QH301-705.5
Spectroscopy
Chemistry
Organic Chemistry
General Medicine
Metabolism
Computer Science Applications
Cell biology
lcsh:Biology (General)
lcsh:QD1-999
Cancer cell
MCF-7 Cells
Tumor Hypoxia
tumor metabolism
Lumen (unit)
Subjects
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