ArticleArchives of toxicology2025
Bridging dimensions: a comparative analysis of 2D and 3D in vitro models for hepatocellular carcinoma research.
Article in Archives of toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed.
- Caffeine in the Context of Sorafenib Chemotherapy: Insights From Experimental Hepatocarcinogenesis.Journal of biochemical and molecular toxicology · 2026Article
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Authors and funding
11 authors.
Funding
Abstract
The tumor microenvironment (TME) influences hepatocellular carcinoma (HCC) behavior and disease progression. Cell-cell dynamics of non-parenchymal components, such as hepatic stellate cells (HSC), are key factors in understanding HCC onset and progression. This study established mono- and co-culture in vitro HCC models in both 2D and 3D configurations to investigate HCC cell behavior at both functional and transcriptional levels. Human HCC C3A cells were co-cultured with human HSC LX2 cells or alone in ultra-low attachment plates to form spheroids (3D) or in a transwell system (2D). In the 2D model, the paracrine signaling of HSC-HCC cells promoted colony formation and HCC cells motility compared to the C3A monolayer, showing a pro-inflammatory transcriptomic signature through a positive regulation of canonical NF-κB pathway. In the 3D model, co-culture spheroids exhibited higher cell viability, enhanced angiogenesis, migration, and extracellular matrix (ECM)-related transcriptomic hallmarks compared to C3A monoculture. Regardless of the configuration, co-culture models shared 74 genes, including angiogenesis, proteolysis and response to wounding functional annotations, indicating a LX2-induced pro-tumoral signature in C3A cells. The 2D vs. 3D comparison revealed that the 3D model enriched proliferation-related genes in monocultured C3A spheroids compared to C3A monolayers, whilst co-culture spheroids showed cholesterol, angiogenesis, migration and ECM annotations compared to co-culture transwell model. These findings reinforce the importance of HSC as key microenvironmental cellular components in HCC and highlight how cellular dynamics modify HCC cell behavior in vitro.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.