ArticleCell death & disease2020
Proteoglycan-4 is correlated with longer survival in HCC patients and enhances sorafenib and regorafenib effectiveness via CD44 in vitro.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Addition of PRG4 to Optimize the Anti-Adhesive Properties of Tissue Barrier SeprafilmAnnals of biomedical engineering · 2026Article
- United multi-omics and machine learning refine regulatory T cell-defined hepatocellular carcinoma subtypes.iScience · 2026Article
- Proteoglycan-4 potentiates the antitumor efficacy of regorafenib in an orthotopic model of hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Multiomics approach provides insight into altered choline metabolism and liver injury in patients with glycogen storage disease type Ia.Scientific reports · 2025Article
- New Hepatocellular Carcinoma (HCC) Primary Cell Cultures as Models for Exploring Personalized Anti-TGF-β Therapies Based on Tumor Characteristics.International journal of molecular sciences · 2025Article
- Integrative analysis of senescence-related genes identifies robust prognostic clusters with distinct features in hepatocellular carcinoma.Journal of advanced research · 2025Article
- Somatostatin receptor-targeted polymeric nanoplatform for efficient CRISPR/Cas9 gene editing to enhance synergistic hepatocellular carcinoma therapy.Journal of nanobiotechnology · 2025Article
- Unveiling complex patterns: An information-theoretic approach to high-order behaviors in microarray data.PloS one · 2025Article
- Targeting cancer-associated fibroblasts/tumor cells cross-talk inhibits intrahepatic cholangiocarcinoma progression via cell-cycle arrest.Journal of experimental & clinical cancer research : CR · 2024Article
- Laminin-332 γ2 Monomeric Chain Promotes Adhesion and Migration of Hepatocellular Carcinoma Cells.Cancers · 2023Article
- Novel insights into the progression and prognosis of the calpain family members in hepatocellular carcinoma: a comprehensive integrated analysis.Frontiers in molecular biosciences · 2023Article
- Crenigacestat blocking notch pathway reduces liver fibrosis in the surrounding ecosystem of intrahepatic CCA viaTGF-β inhibition.Journal of experimental & clinical cancer research : CR · 2022Article
- Proteoglycans in Cancer: Friends or Enemies? A Special Focus on Hepatocellular Carcinoma.Cancers · 2022Review
- DYRK1A suppression attenuates HIF‑1α accumulation and enhances the anti‑liver cancer effects of regorafenib and sorafenib under hypoxic conditions.International journal of oncology · 2022Article
- Acyl-CoA Binding Domain Containing 4 Polymorphism rs4986172 and Expression Can Serve as Overall Survival Biomarkers for Hepatitis B Virus-Related Hepatocellular Carcinoma Patients After Hepatectomy.Pharmacogenomics and personalized medicine · 2022Article
- Aging-related features predict prognosis and immunotherapy efficacy in hepatocellular carcinoma.Frontiers in immunology · 2022Article
- Proteoglycan-4 predicts good prognosis in patients with hepatocellular carcinoma receiving transcatheter arterial chemoembolization and inhibits cancer cell migrationFrontiers in oncology · 2022Article
- CD44 Glycosylation as a Therapeutic Target in Oncology.Frontiers in oncology · 2022Review
- Selenium sulfide disrupts the PLAGL2/C-MET/STAT3-induced resistance against mitochondrial apoptosis in hepatocellular carcinoma.Clinical and translational medicine · 2021Article
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Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sorafenib and regorafenib administration is among the preferential approaches to treat hepatocellular carcinoma (HCC), but does not provide satisfactory benefits. Intensive crosstalk occurring between cancer cells and other multiple non-cancerous cell subsets present in the surrounding microenvironment is assumed to affect tumor progression. This interplay is mediated by a number of soluble and structural extracellular matrix (ECM) proteins enriching the stromal milieu. Here we assess the HCC tumor expression of the ECM protein proteoglycan 4 (PRG4) and its potential pharmacologic activity either alone, or in combination with sorafenib and regorafenib. PRG4 mRNA levels resulted strongly correlated with increased survival rate of HCC patients (p = 0.000) in a prospective study involving 78 HCC subjects. We next showed that transforming growth factor beta stimulates PRG4 expression and secretion by primary human HCC cancer-associated fibroblasts, non-invasive HCC cell lines, and ex vivo specimens. By functional tests we found that recombinant human PRG4 (rhPRG4) impairs HCC cell migration. More importantly, the treatment of HCC cells expressing CD44 (the main PRG4 receptor) with rhPRG4 dramatically enhances the growth-limiting capacity of sorafenib and regorafenib, whereas not significantly affecting cell proliferation per se. Conversely, rhPRG4 only poorly potentiates drug effectiveness on low CD44-expressing or stably CD44-silenced HCC cells. Overall, these data suggest that the physiologically-produced compound PRG4 may function as a novel tumor-suppressive agent by strengthening sorafenib and regorafenib effects in the treatment of HCC.
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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.