ArticleInternational journal of oncology2020
ADAM17-regulated CX3CL1 expression produced by bone marrow endothelial cells promotes spinal metastasis from hepatocellular carcinoma.
Article in International journal of oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- The Role of Cytokines in the Metastasis of Solid Tumors to the Spine: Systematic Review.International journal of molecular sciences · 2023Pooled it
- The liver-bone axis: an emerging player in disease pathogenesis and therapeutic intervention.Science China. Life sciences · 2026Review
- Review
- CX3CL1/CX3CR1 axis in liver disease: context-dependent roles and balance.Frontiers in immunology · 2026Review
- Chemokines: Orchestration of the Tumor Microenvironment and Control of Hepatocellular Carcinoma Progression.Cancer medicine · 2025Review
- HCC-derived CX3CL1 affects hepatocellular carcinoma prognosis and CX3CR1 + MDSC infiltration.European journal of medical research · 2025Article
- Article
- CX3CL1/Fractalkine: A Potential Biomarker for Liver Fibrosis in Chronic HBV Infection.Current issues in molecular biology · 2024Article
- Signaling molecules in the microenvironment of hepatocellular carcinoma.Functional & integrative genomics · 2024Review
- CX3CL1 (Fractalkine)-CX3CR1 Axis in Inflammation-Induced Angiogenesis and Tumorigenesis.International journal of molecular sciences · 2024Review
- Role of tumor-associated macrophages in hepatocellular carcinoma: impact, mechanism, and therapy.Frontiers in immunology · 2024Review
- The role of vascular and lymphatic networks in bone and joint homeostasis and pathology.Frontiers in endocrinology · 2024Review
- High glucose-induced NCAPD2 upregulation promotes malignant phenotypes and regulates EMT via the Wnt/β-catenin signaling pathway in HCC.American journal of cancer research · 2024Article
- Article
- Blockage of CacyBP inhibits macrophage recruitment and improves anti-PD-1 therapy in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2023Article
- Role of chemokines in the crosstalk between tumor and tumor-associated macrophages.Clinical and experimental medicine · 2023Review
- Predictive Biomarkers for Immune-Checkpoint Inhibitor Treatment Response in Patients with Hepatocellular Carcinoma.International journal of molecular sciences · 2023Review
- Nucleus Pulposus Cells Induce M2 Polarization of RAW264.7 via CX3CL1/CX3CR1 Pathway and M2 Macrophages Promote Proliferation and Anabolism of Nucleus Pulposus Cells.Stem cells international · 2023Article
- Osteoid cell-derived chemokines drive bone-metastatic prostate cancer.Frontiers in oncology · 2023Review
- Solitary extrahepatic hepatocellular carcinoma in vertebrae without a primary lesion in the liver might originate from bone marrow: a case report and new hypothesis based on a review of the literature and the latest findings.Clinical journal of gastroenterology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinal metastasis occurs in 50‑75% of bone metastases caused by hepatocellular carcinoma (HCC), and HCC‑derived spinal metastasis can lead to a less favorable prognosis. Recently, several studies have demonstrated that C‑X3‑C motif chemokine ligand 1 (CX3CL1) is closely associated with cancer metastasis, and its secretion is modulated by a disintegrin and metalloproteinase 17 (ADAM17). Bone marrow endothelial cells (BMECs) are an essential component of bone marrow. However, little is known about the roles in and effects of BMECs on HCC spinal metastasis. The present study demonstrated that CX3CL1 and C‑X‑C motif chemokine receptor 3 (CXCR3) expression was upregulated in HCC spinal metastases, and that CX3CL1 promoted the migration and invasion of HCC cells to the spine. Western blot analysis revealed that the Src/protein tyrosine kinase 2 (PTK2) axis participated in CX3CL1‑induced HCC cell invasion and migration. CX3CL1 also increased the expression of M2 macrophage markers in THP‑1 monocytes. BMECs promoted the migration and invasion of Hep3B and MHCC97H cells by secreting soluble CX3CL1, whereas the neutralization of CX3CL1 inhibited this enhancement. CX3CL1 enhanced the activation of the phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit alpha (PIK3CA)/AKT serine/threonine kinase 1 (AKT1) and Ras homolog family member A (RHOA)/Rho associated coiled‑coil containing protein kinase 2 (ROCK2) signaling pathways through the Src/PTK2 signaling pathway. Furthermore, ADAM17 was activated by mitogen‑activated protein kinase (MAPK)z14 in BMECs and significantly promoted the secretion of CX3CL1. HCC cells enhanced the recruitment and proliferation of BMECs. The overexpression of CX3CR1 facilitated the spinal metastasis of HCC in a mouse model in vivo. In addition, in vivo experiments revealed that BMECs promoted the growth of HCC in the spine. The present study demonstrated that CX3CL1 participates in HCC spinal metastasis, and that BMECs play an important role in the regulation of CX3CL1 in the spinal metastatic environment.
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