ArticleScientific reports2021
Continual proteomic divergence of HepG2 cells as a consequence of long-term spheroid culture.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
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- Development and Validation of a Scaffold-Free Human Multilineage Spheroid Model for Early Stage Cholangiopathies Driven by Cholangiocyte Senescence.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Utility of Multicellular Spheroids for Investigating Mechanisms of Chemoresistance in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- Polyacrylamide Hydrogels with Reversibly Photocontrolled Stiffness for 2D Mechanobiology.ACS applied materials & interfaces · 2025Article
- 3D Biomimetic Liver Cancer Model: Diethylnitrosamine-Induced Proteomic Dysregulations in Stromal-Epithelial Milieu.bioRxiv : the preprint server for biology · 2025Article
- Hepatic spheroid-on-a-chip: Fabrication and characterization of a spheroid-basedBiomicrofluidics · 2024Article
- SPRED2: A Novel Regulator of Epithelial-Mesenchymal Transition and Stemness in Hepatocellular Carcinoma Cells.International journal of molecular sciences · 2023Article
- The Performance of HepG2 and HepaRG Systems through the Glass of Acetaminophen-Induced Toxicity.Life (Basel, Switzerland) · 2021Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Three-dimensional models are considered a powerful tool for improving the concordance between in vitro and in vivo phenotypes. However, the duration of spheroid culture may influence the degree of correlation between these counterparts. When using immortalised cell lines as model systems, the assumption for consistency and reproducibility is often made without adequate characterization or validation. It is therefore essential to define the biology of each spheroid model by investigating proteomic dynamics, which may be altered relative to culture duration. As an example, we assessed the influence of culture duration on the relative proteome abundance of HepG2 cells cultured as spheroids, which are routinely used to model aspects of the liver. Quantitative proteomic profiling of whole cell lysates labelled with tandem-mass tags was conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In excess of 4800 proteins were confidently identified, which were shared across three consecutive time points over 28 days. The HepG2 spheroid proteome was divergent from the monolayer proteome after 14 days in culture and continued to change over the successive culture time points. Proteins representing the recognised core hepatic proteome, cell junction, extracellular matrix, and cell adhesion proteins were found to be continually modulated.
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