ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
Small Extracellular Vesicle-Derived vWF Induces a Positive Feedback Loop between Tumor and Endothelial Cells to Promote Angiogenesis and Metastasis in Hepatocellular Carcinoma.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.
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
24 citing papers in PubMed.
- Article
- Unlocking the Future of Hepatocellular Carcinoma Early Diagnosis: The Promise of Extracellular Vesicle Biomarkers.Journal of clinical and translational hepatology · 2026Review
- Developing blood extracellular vesicle protein biomarkers for hepatocellular carcinoma: mechanisms, methods, and translation.Journal of nanobiotechnology · 2026Review
- Targeting the FGF19/FGFR4 positive feedback loop to disrupt ERK-mediated tumor progression in head and neck cancer.Journal of translational medicine · 2026Article
- Tumor-associated macrophages display differential protein cargo sorting in extracellular vesicles associated with poor survival in ovarian cancer.Molecular medicine (Cambridge, Mass.) · 2026Article
- Plasma small-extracellular vesicles' proteomic signature in neoadjuvant chemotherapy-naïve breast cancer patients.PloS one · 2026Article
- Article
- Lipid metabolism and lipid signaling in extracellular vesicles ontogeny: from biogenesis to functional execution.Journal of nanobiotechnology · 2025Review
- Natural and Bioengineered Extracellular Vesicles in Diagnosis, Monitoring and Treatment of Cancer.ACS nano · 2025Review
- FBXO22 promotes HCC angiogenesis and metastasis via RPS5/AKT/HIF-1α/VEGF-A signaling axis.Cancer gene therapy · 2025Article
- Breaking the premetastatic niche barrier: the role of endothelial cells and therapeutic strategies.Theranostics · 2025Review
- Hub Genes Involved in the Progression of Nonalcoholic Fatty Liver Disease to Hepatocellular Carcinoma.Current medicinal chemistry · 2025Article
- PCBP2-dependent secretion of miRNAs via extracellular vesicles contributes to the EGFR-driven angiogenesis.Theranostics · 2025Article
- Revealing the Potential of Solamargine for Anti Metastasis and Angiogenesis Inhibition in Nasopharyngeal Carcinoma.Journal of inflammation research · 2025Article
- Multidimensional insights into exosomes in hepatocellular carcinoma: from genesis to clinical application.Frontiers in immunology · 2025Review
- Extracellular Vesicles in Viral Liver Diseases.Viruses · 2024Review
- Multi-stage mechanisms of tumor metastasis and therapeutic strategies.Signal transduction and targeted therapy · 2024Review
- SOX4-BMI1 axis promotes non-small cell lung cancer progression and facilitates angiogenesis by suppressing ZNF24.Cell death & disease · 2024Article
- Role of extracellular vesicle-associated proteins in the progression, diagnosis, and treatment of hepatocellular carcinoma.Cell & bioscience · 2024Review
- From Genesis to Old Age: Exploring the Immune System One Cell at a Time with Flow Cytometry.Biomedicines · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors.
Funding
Abstract
Hepatocellular carcinoma (HCC) is a hypervascular malignancy by which its growth and dissemination are largely driven by the modulation of tumor-derived small extracellular vesicles (sEVs). Proteomic profiling of circulating sEVs of control individuals and HCC patients identifies von Willibrand factor (vWF) to be upregulated progressively along HCC stages. Elevated sEV-vWF levels are found in a larger cohort of HCC-sEV samples and metastatic HCC cell lines compared to their respective normal counterparts. Circulating sEVs of late-stage HCC patients markedly augment angiogenesis, tumor-endothelial adhesion, pulmonary vascular leakiness, and metastasis, which are significantly compromised by anti-vWF antibody. The role of vWF is further corroborated by the enhanced promoting effect of sEVs collected from vWF-overexpressing cells. sEV-vWF modulates endothelial cells through an elevated level of vascular endothelial growth factor A (VEGF-A) and fibroblast growth factor 2 (FGF2). Mechanistically, secreted FGF2 elicits a positive feedback response in HCC via the FGFR4/ERK1 signaling pathway. The co-administration of anti-vWF antibody or FGFR inhibitor significantly improves the treatment outcome of sorafenib in a patient-derived xenograft mouse model. This study reveals mutual stimulation between HCC and endothelial cells by tumor-derived sEVs and endothelial angiogenic factors, facilitating angiogenesis and metastasis. It also provides insights into a new therapeutic strategy involving blocking tumor-endothelial intercellular communication.
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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.