ArticleScientific reports2019
Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- From steatosis to metastasis: microenvironmental reprogramming of the liver in metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Targeting SMYD2 improves immunotherapy response in experimental hepatocellular carcinoma.Molecular therapy. Oncology · 2026Article
- 4-methylumbelliferone attenuates amyloid pathology and learning deficits in the APP/PS1 mouse model.bioRxiv : the preprint server for biology · 2026Article
- Low-dose DOX-polygodial nanosystem modulates the CD47/CALR axis for safer triple negative breast cancer treatment.Nanoscale advances · 2026Article
- Targeting CD44-Hyaluronic Acid Signalling in Obesity Treatment: Insights from Small Molecules and Nanobioconjugates.Nutrition and metabolic insights · 2026Review
- Hepatocellular carcinoma stem cells: the current state of small molecule-based inhibitors.Cell death & disease · 2025Review
- Endogenous Hyaluronan Promotes Intestinal Homeostasis and Protects against Murine Necrotizing Enterocolitis.Cells · 2024Article
- Histologic, immunohistochemical, and in situ hybridization study of myxoid stroma in feline oral squamous cell carcinoma.The Journal of veterinary medical science · 2024Article
- Knockdown of Hyaluronan synthase 2 suppresses liver fibrosis in mice via induction of transcriptomic changes similar to 4MU treatment.Scientific reports · 2024Article
- Unveiling the Role of Mechanical Microenvironment in Hepatocellular Carcinoma: Molecular Mechanisms and Implications for Therapeutic Strategies.International journal of biological sciences · 2024Review
- Cancer stem cells and their niche in cancer progression and therapy.Cancer cell international · 2023Review
- Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments.Molecular cancer · 2023Review
- The extracellular matrix alteration, implication in modulation of drug resistance mechanism: friends or foes?Journal of experimental & clinical cancer research : CR · 2022Review
- Dysregulated glucuronic acid metabolism exacerbates hepatocellular carcinoma progression and metastasis through the TGFβ signalling pathway.Clinical and translational medicine · 2022Article
- Inhibition of hyaluronan secretion by novel coumarin compounds and chitin synthesis inhibitors.Glycobiology · 2021Article
- Immunotherapy against programmed death-1/programmed death ligand 1 in hepatocellular carcinoma: Importance of molecular variations, cellular heterogeneity, and cancer stem cells.World journal of stem cells · 2021Review
- Integration of mechanical and ECM microenvironment signals in the determination of cancer stem cell states.Current stem cell reports · 2021Article
- Serum Anti-14-3-3 Zeta Autoantibody as a Biomarker for Predicting Hepatocarcinogenesis.Frontiers in oncology · 2021Article
- Targeting the Tumor Extracellular Matrix by the Natural Molecule 4-Methylumbelliferone: A Complementary and Alternative Cancer Therapeutic Strategy.Frontiers in oncology · 2021Review
- Hepatic Stellate Cell-Macrophage Crosstalk in Liver Fibrosis and Carcinogenesis.Seminars in liver disease · 2020Review
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyaluronic acid (HA) is a glycosaminoglycan of extracellular matrix related to cell surface which interacts with various cell types. To understand the role of HA during hepatocarcinogenesis, we assessed the effect of the inhibition of HA deposition and its association with heterogeneous hepatocellular carcinoma (HCC) cells. In this study, we used transgenic mice C57BL/6J-Tg(Alb1HBV)44Bri/J (HBV-TG) and normal C57BL/6 J (WT) for in vivo study, while HCC cells Huh7 and JHH6 as in vitro models. Both models were treated with an HA inhibitor 4-methylumbelliferone (4MU). We observed that 4MU treatments in animal model down-regulated the mRNA expressions of HA-related genes Has3 and Hyal2 only in HBV-TG but not in normal WT. As observed in vivo, in HCC cell lines, the HAS2 mRNA expression was down-regulated in Huh7 while HAS3 in JHH6, both with or without the presence of extrinsic HA. Interestingly, in both models, the expressions of various cancer stem cells (CD44, CD90, CD133, and EpCAM) were also decreased. Further, histological analysis showed that 4MU treatment with dose 25 mg/kg/day reduced fibrosis, inflammation, and steatosis in vivo, in addition to be pro-apoptotic. We concluded that the inhibition of HA reduced the expressions of HA-related genes and stem cells markers in both models, indicating a possible modulation of cells-to-cells and cells-to-matrix interaction.
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