ArticleScientific reports2016
Activated hepatic stellate cells play pivotal roles in hepatocellular carcinoma cell chemoresistance and migration in multicellular tumor spheroids.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 116 citations in OpenAlex.
- Hepatic stellate cells promote structural and functional remodeling of three-dimensional hepatocellular carcinoma coculture spheroids.Molecular biology reports · 2026Article
- Label-Free Hyperspectral Raman Imaging and Analysis of a 3D Spheroid Model for Liver Fibrosis Study.Chemical & biomedical imaging · 2026Article
- Glimpse into the role of Kupffer cells in a spheroid model of metabolic dysfunction-associated steatohepatitis (MASH).Biology open · 2026Article
- Integrating Transcriptomics and 3D Spheroid Models Reveals Microenvironment-Dependent Purinergic Modulation in Hepatocellular Carcinoma.Metabolites · 2026Article
- Sequential nanotheranostics based on hollow mesoporous silica loaded doxorubicin and seed kernel extract fromDrug delivery · 2025Article
- Targeting collagen to optimize cancer immunotherapy.Experimental hematology & oncology · 2025Review
- Innovative Approaches to NAFLD: Exploring the Role of Nicotinamide in Multicellular Microtissue Models of Liver Fibrosis.Journal of cellular and molecular medicine · 2025Article
- Premixing enables loading of long RNA in cubic phase lipid nanoparticles.Nature communications · 2025Article
- Advances in Tumor Microenvironment and Immunotherapeutic Strategies for Hepatocellular Carcinoma.Oncology research · 2025Review
- The effects of simvastatin-loaded nanoliposomes on human multilineage liver fibrosis microtissue.Journal of cellular and molecular medicine · 2024Article
- Bacteriophage-based particles carrying the TNF-related apoptosis-inducing ligand (TRAIL) gene for targeted delivery in hepatocellular carcinoma.Nanoscale · 2024Article
- Linking fatty liver diseases to hepatocellular carcinoma by hepatic stellate cells.Journal of the National Cancer Center · 2024Review
- Inhibition of DNMT3B expression in activated hepatic stellate cells overcomes chemoresistance in the tumor microenvironment of hepatocellular carcinoma.Scientific reports · 2024Article
- Changes of immune microenvironment in head and neck squamous cell carcinoma in 3D-4-culture compared to 2D-4-culture.Journal of translational medicine · 2023Article
- Critical Review in Designing Plant-Based Anticancer Nanoparticles against Hepatocellular Carcinoma.Pharmaceutics · 2023Review
- Spatiotemporal regulation of cholangiocarcinoma growth and dissemination by peritumoral myofibroblasts in a Vcam1-dependent manner.Oncogene · 2023Article
- Deciphering the underlying mechanism of liver diseases through utilization of multicellular hepatic spheroid models.BMB reports · 2023Review
- Fibroblasts as Turned Agents in Cancer Progression.Cancers · 2023Review
- A hepatoprotective role of peritumoral non-parenchymal cells in early liver tumorigenesis.Disease models & mechanisms · 2023Article
- Extracellular vesicle‑mediated miR‑126‑3p transfer contributes to inter‑cellular communication in the liver tumor microenvironment.International journal of oncology · 2023Article
1 more citing papers are in PubMed but not listed here.
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6 authors at 3 institutions in 1 country.
Funding
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Abstract
Most Hepatocellular carcinoma (HCC) are resistant to conventional chemotherapeutic agents and remain an unmet medical need. Recently, multiple studies on the crosstalk between HCC and their tumor microenvironment have been conducted to overcome chemoresistance in HCC. In this study, we formed multicellular tumor spheroids (MCTS) to elucidate the mechanisms of environment-mediated chemoresistance in HCC. We observed that hepatic stellate cells (HSCs) in MCTS significantly increased the compactness of spheroids and exhibited strong resistance to sorafenib and cisplatin relative to other types of stromal cells. Increased collagen 1A1 (COL1A1) expression was apparent in activated HSCs but not in fibroblasts or vascular endothelial cells in MCTS. Additionally, COL1A1 deficiency, which was increased by co-culture with HSCs, decreased the cell-cell interactions and thereby increased the therapeutic efficacy of anticancer therapies in MCTS. Furthermore, losartan, which can inhibit collagen I synthesis, attenuated the compactness of spheroids and increased the therapeutic efficacy of anticancer therapies in MCTS. Meanwhile, activated HSCs facilitated HCC migration by upregulating matrix metallopeptidase 9 (MMP9) in MCTS. Collectively, crosstalk between HCC cells and HSCs promoted HCC chemoresistance and migration by increasing the expression of COL1A1 and MMP9 in MCTS. Hence, targeting HSCs might represent a promising therapeutic strategy for liver cancer therapy.
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