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. 2023 Feb 1;24(3):2717. doi: 10.3390/ijms24032717

Table 1.

Experimental discrepant result between 2D and 3D cultures.

Discrepancy between 3D vs. 2D Culture 3D Culture Technique Cancer Type Related Hallmark of Cancer Metabolism Refs.
Increased glycolysis upstream metabolites and TCA 3D silica scaffolds (CellBed®) Prostate
Bladder
Deregulated uptake of glucose and amino acids
Use of carbon metabolism to support biosynthesis
[42]
HIF1a stabilization increases ATP production and sustains NAD(P)H/NAD(P)+ ratio Organoids Ovarian Deregulated uptake of glucose and amino acids
Increased demand of electron acceptors
Elevated reliance on oxidative stress protection mechanisms
[44]
Spheroids Ovarian
Breast
Colon
Liver
[45,46,47,48]
3D bioprinting Breast
Colon
[49,50]
Magnetic 3D bioprinted spheroids Pancreatic
Lung
[51]
Increased amino acid production 3D silica scaffolds (CellBed®) Prostate
Bladder
Deregulated uptake of glucose and amino acids
Use of carbon metabolism to support biosynthesis
Increased demand for nitrogen
Increased demand of electron acceptors
Elevated reliance on oxidative stress protection mechanisms
[42]
Increased glutamate synthesis from glutamine 3D scaffolds (SeedEZ™) Head and neck Increased demand for nitrogen
Increased demand of electron acceptors
Elevated reliance on oxidative stress protection mechanisms
[52]
Increased amino acid acquisition and biosynthesis Organotypic cultures Colorectal
Lung
Breast
Ovarian
Deregulated uptake of glucose and amino acids
Use of carbon metabolism to support biosynthesis
Increased demand for nitrogen
[43]
Increased interconnexion between TCA, urea cycle, amino acids, and pyruvate synthesis Organotypic cultures Colorectal
Lung
Breast
Ovarian
Use of carbon metabolism to support biosynthesis
Increased demand for nitrogen
[43]
Reduced dependence on glutamine acquisition Organotypic cultures Colorectal
Lung
Breast
Ovarian
Deregulated uptake of glucose and amino acids
Use of carbon metabolism to support biosynthesis
Increased demand for nitrogen
[43]
Increased dependence on mTORC1 activation Microwell chip Bladder Use of carbon metabolism to support biosynthesis [53]
Spheroids Ovarian
Gastric
[54,55]
Autophagy employment as survival strategy 3D culture basement membrane extracts reduced growth factor (Cultrex) Breast Use of opportunistic models of nutrient acquisition
Elevated reliance on oxidative stress protection mechanisms
[56]
Culture in low attachment plates Prostate [57]
Use of macropinocytosis as a nutrient acquisition strategy Spheroids Womb
Epidermoid carcinoma
Use of opportunistic models of nutrient acquisition [58]
Use of entosis as a nutrient acquisition strategy Organoid Ovary
Colon
Use of opportunistic models of nutrient acquisition
Increased demand of electron acceptors
[44,59]
Spheroids Ovary
Colon
Breast
Liver
[45,46,47,48]
3D bioprinting Colon
Breast
Lung
Pancreatic
[49,50,51]
Alterations in the metabolic profile as a response to the hypoxia-induced redox stress 3D silica scaffolds (CellBed®) Prostate
Bladder
Increased demand of electron acceptors
Elevated reliance on oxidative stress protection mechanisms
[42]
Organoids Ovarian
Colon
[44,54,60]
Spheroids Ovarian [45,61]
3D bioprinting Lung
Pancreatic
Colon
[48,49]
Reutilization of nitrogen from urea cycle Spheroids Pancreatic Increased demand for nitrogen [62]
Organoids Breast [63]
Collagen composition of extracellular matrix increases cancer cell invasiveness 3D collagen microchannels Pancreatic Heterogeneity of metabolic adaptations
Metabolic interactions with the tumour microenvironment
[64]
Spheroids Breast [65]
Nutritional support by other cell populations Microfluidic device and scaffolds
3D scaffolds
Pancreatic
Prostate
Heterogeneity of metabolic adaptations
Metabolic interactions with the tumour microenvironment
[39,41]