ArticleJournal of experimental & clinical cancer research : CR2016
EphA1 activation promotes the homing of endothelial progenitor cells to hepatocellular carcinoma for tumor neovascularization through the SDF-1/CXCR4 signaling pathway.
Article in Journal of experimental & clinical cancer research : CR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Targeting tumor vascular endothelial cells for hepatocellular carcinoma treatment.World journal of gastroenterology · 2025Article
- TScience advances · 2025Article
- LncRNA EBLN3P/microRNA-323a-3p/EphA1 axis affects the biological function of hepatocellular carcinoma cells.Discover oncology · 2025Article
- IGF-1 secreted by mesenchymal stem cells affects the function of lymphatic endothelial progenitor cells: a potential strategy for the treatment of lymphedema.Frontiers in genetics · 2025Article
- Article
- Optogenetic Regulation of EphA1 RTK Activation and Signaling.bioRxiv : the preprint server for biology · 2024Article
- Advances and current concepts on Eph receptors and ephrins in upper digestive tract cancers.Frontiers in oncology · 2024Review
- A pan-cancer analysis of EphA family gene expression and its association with prognosis, tumor microenvironment, and therapeutic targets.Frontiers in oncology · 2024Article
- Ephrin-Eph receptor tyrosine kinases for potential therapeutics against hepatic pathologies.Journal of cell communication and signaling · 2023Review
- EphA1 Activation Induces Neuropathological Changes in a Mouse Model of Parkinson's Disease Through the CXCL12/CXCR4 Signaling Pathway.Molecular neurobiology · 2021Article
- Emerging Importance of Chemokine Receptor CXCR4 and Its Ligand in Liver Disease.Frontiers in cell and developmental biology · 2021Review
- Sulfatase 2-Induced Cancer-Associated Fibroblasts Promote Hepatocellular Carcinoma Progression via Inhibition of Apoptosis and Induction of Epithelial-to-Mesenchymal Transition.Frontiers in cell and developmental biology · 2021Article
- Association Between EphA1 and Tumor Microenvironment in Gastric Carcinoma and its Clinical Significance.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Combined Transplantation of Adipose Tissue-Derived Stem Cells and Endothelial Progenitor Cells Improve Diabetic Erectile Dysfunction in a Rat Model.Stem cells international · 2020Article
- Roles of EphA1/A2 and ephrin-A1 in cancer.Cancer science · 2019Review
- TCF12 promotes the tumorigenesis and metastasis of hepatocellular carcinoma via upregulation of CXCR4 expression.Theranostics · 2019Article
- KAI1/CD82 Genetically Engineered Endothelial Progenitor Cells Inhibit Metastasis of Human Nasopharyngeal Carcinoma in a Mouse Model.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Potential Role of CXCR4 Targeting in the Context of Radiotherapy and Immunotherapy of Cancer.Frontiers in immunology · 2018Review
- Role of C-X-C chemokine ligand 12/C-X-C chemokine receptor 4 in the progression of hepatocellular carcinoma.Oncology letters · 2017Article
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEndothelial progenitor cells (EPCs) can migrate to the tumor tissue and enhance the angiogenesis of hepatocellular carcinoma (HCC); thus, they are associated with a poor prognosis. However, the specific molecular mechanism underlying the homing of EPCs to the HCC neovasculature remains unrevealed.
methodsCo-culture experiments of endothelial progenitor cells with HCC cells with modulation of EphA1 were performed in vitro. Using EPCs as angiogenic promoters by injecting them into HCC xenograft-bearing nude mice via their tail veins to test homing ability of EPCs changed according to different EphA1 level in HCC xenograft.
resultsIn this study, we found that the up-regulation of EphA1 expression in HCC cells could affect not only the chemotaxis of EPCs to tumor cells and endothelial cells (ECs) but also the tube formation ability of EPCs in a paracrine fashion. Further, we revealed that the increased expression of EphA1 in HCC cells led to an increased SDF-1 concentration in the tumor microenvironment, which in turn activated the SDF-1/CXCR4 axis and enhanced the recruitment of EPCs to HCC. In addition, the EphA1-activated SDF-1 expression and secretion was partially mediated by the PI3K and mTOR pathways. In vivo experiments demonstrated that blocking EphA1/SDF-1/CXCR4 signaling significantly inhibited the growth of HCC xenografts. Using immunohistochemistry and immunofluorescence assays, we verified that the inhibition of tumor angiogenesis was at least partially caused by the decreased number of EPCs homing to tumor tissue.
conclusionsOur findings indicate that targeting the EphA1/SDF-1 signaling pathway might be a therapeutic anti-angiogenesis approach for treating HCC.
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