ArticlePloS one2013
Hepatic stellate cells secreted hepatocyte growth factor contributes to the chemoresistance of hepatocellular carcinoma.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 71 citations in OpenAlex.
- Hedyotis diffusa Willd suppresses hepatocellular carcinoma tumor-stromal interactions by inactivating cancer-associated hepatic stellate cells.Journal of gastrointestinal oncology · 2026Article
- Functions and clinical implications of the liver microenvironment in hepatic uveal melanoma metastases.Cancer metastasis reviews · 2025Review
- Piezo1: the Potential Novel Target for Radiation-induced Liver Fibrosis by Regulating FAP + fibroblasts.Molecular and cellular biochemistry · 2025Review
- Cancer stem cells in hepatocellular carcinoma: therapy resistance and emerging treatments.Frontiers in immunology · 2025Review
- Inactivation of ERK1/2 in cancer-associated hepatic stellate cells suppresses cancer-stromal interaction by regulating extracellular matrix in fibrosis.American journal of cancer research · 2024Article
- Extracellular vesicle‑mediated miR‑126‑3p transfer contributes to inter‑cellular communication in the liver tumor microenvironment.International journal of oncology · 2023Article
- Mechanisms of Resistance to Immunotherapy in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2023Review
- The rationale for treating uveal melanoma with adjuvant melatonin: a review of the literature.BMC cancer · 2022Review
- Current Perspectives on the Immunosuppressive Niche and Role of Fibrosis in Hepatocellular Carcinoma and the Development of Antitumor Immunity.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2022Review
- Role of Biobanks for Cancer Research and Precision Medicine in Hepatocellular Carcinoma.Journal of gastrointestinal cancer · 2021Review
- Review
- Emerging Regulatory Mechanisms Involved in Liver Cancer Stem Cell Properties in Hepatocellular Carcinoma.Frontiers in cell and developmental biology · 2021Review
- Inhibiting IRE1α-endonuclease activity decreases tumor burden in a mouse model for hepatocellular carcinoma.eLife · 2020Article
- Cancer stemness in hepatocellular carcinoma: mechanisms and translational potential.British journal of cancer · 2020Review
- The Cancer Stem Cell in Hepatocellular Carcinoma.Cancers · 2020Review
- Inhibition of M2-like macrophages by all-trans retinoic acid prevents cancer initiation and stemness in osteosarcoma cells.Acta pharmacologica Sinica · 2019Article
- The Role of Fibrosis and Liver-Associated Fibroblasts in the Pathogenesis of Hepatocellular Carcinoma.International journal of molecular sciences · 2019Review
- 8-bromo-7-methoxychrysin suppress stemness of SMMC-7721 cells induced by co-culture of liver cancer stem-like cells with hepatic stellate cells.BMC cancer · 2019Article
- Effects of low-density lipoprotein docosahexaenoic acid nanoparticles on cancer stem cells isolated from human hepatoma cell lines.Molecular biology reports · 2018Article
- Sulfasalazine attenuates evading anticancer response of CD133-positive hepatocellular carcinoma cells.Journal of experimental & clinical cancer research : CR · 2017Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As the main source of extracellular matrix proteins in tumor stroma, hepatic stellate cells (HSCs) have a great impact on biological behaviors of hepatocellular carcinoma (HCC). In the present study, we have investigated a mechanism whereby HSCs modulate the chemoresistance of hepatoma cells. We used human HSC line lx-2 and chemotherapeutic agent cisplatin to investigate their effects on human HCC cell line Hep3B. The results showed that cisplatin resistance in Hep3B cells was enhanced with LX-2 CM (cultured medium) exposure in vitro as well as co-injection with LX-2 cells in null mice. Meanwhile, in presence of LX-2 CM, Hep3B cells underwent epithelial to mesenchymal transition (EMT) and upregulation of cancer stem cell (CSC) -like properties. Besides, LX-2 cells synthesized and secreted hepatic growth factor (HGF) into the CM. HGF receptor tyrosine kinase mesenchymal-epithelial transition factor (Met) was activated in Hep3B cells after LX-2 CM exposure. The HGF level of LX-2 CM could be effectively reduced by using HGF neutralizing antibody. Furthermore, depletion of HGF in LX-2 CM abolished its effects on activation of Met as well as promotion of the EMT, CSC-like features and cisplatin resistance in Hep3B cells. Collectively, secreting HGF into tumor milieu, HSCs may decrease hepatoma cells sensitization to chemotherapeutic agents by promoting EMT and CSC-like features via HGF/Met signaling.
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