ArticleCell communication and signaling : CCS2023
M2 macrophage-secreted exosomes promote metastasis and increase vascular permeability in hepatocellular carcinoma.
Article in Cell communication and signaling : CCS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
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Who cites it
110 citing papers in PubMed, 129 citations in OpenAlex.
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- Single-Cell Transcriptomics Dissects the Molecular Mechanism by Which Macrophage Polarization Drives Hepatocellular Carcinoma Metastasis Through Crosstalk with Emt-Tumor Microenvironment.Digestive diseases and sciences · 2026Article
- M2 macrophage-derived exosomal EHF transcriptionally activates FGFR1 to promote malignant phenotypes and glycolysis in NSCLC.Journal of bioenergetics and biomembranes · 2026Article
- Exosomal PKM2 from AML cells reprograms endothelial metabolism to promote angiogenesis and chemoresistance.Functional & integrative genomics · 2026Article
- Macrophage Notch1 drives hepatocyte ferroptosis via the exosomal miR-142a-3p/TIPE2 axis to promote MASH progression.Cell & bioscience · 2026Article
- APOC1⁺IFI30⁺ TAMs orchestrate colorectal cancer liver metastasis by coupling cholesterol biosynthesis with secretion of immunosuppressive factors.Cellular and molecular life sciences : CMLS · 2026Article
- Hepatocellular carcinoma metastasis-immune microenvironment crosstalk: emerging mechanisms and immunotherapy.Cellular & molecular biology letters · 2026Review
- Dissecting the Transcriptomic Profile of CD163Liver cancer · 2026Article
- Tumor-Derived Exosomal TAGLN2 Promotes Metastasis by Inducing Vascular Permeability and Angiogenesis via the NRP1/SEMA4D/YAP Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Look Who Is Talking: Extracellular Vesicles as Mediators of Intercellular and Interorgan Communication.Comprehensive Physiology · 2026Review
- Study on the effects and mechanisms of M2 macrophages on PYCR1-promoted biological behavior of hepatocellular carcinoma cells.Scientific reports · 2026Article
- Atherosclerotic plaque-derived extracellular vesicles mediate smooth muscle cell phenotypic switching and promote vascular remodeling : EVs promote VSMC phenotypic switching.Cellular and molecular life sciences : CMLS · 2026Article
- Chemokine Networks in Blood-Brain Barrier Regulation: Bidirectional Mechanisms, Clinical Translation, and Precision Therapeutic Prospects.Biomolecules · 2026Review
- Cuprotosis-related gene subtypes, prognostic modeling, and tumor microenvironment remodeling in breast cancer.Translational cancer research · 2026Article
- Molecular mechanisms of tumor-associated macrophages in hepatocellular carcinoma development and therapy.World journal of gastroenterology · 2026Review
- M2 macrophage-derived extracellular vesicles induce EMT-like transcriptional reprogramming in colorectal cancer cells via upregulation of FAM83A.Scientific reports · 2026Article
- Engineered M2 macrophage-derived extracellular vesicles reprogram mitochondrial metabolism to alleviate temporomandibular joint cartilage degeneration.Materials today. Bio · 2026Article
- Somatostatin Effect on Growth Factors in Hepatocellular Carcinoma.Current issues in molecular biology · 2026Article
- Tumor-derived exosomes carry LCN2 to block Nedd4-1-mediated SR-BI ubiquitination, inducing M2 macrophage polarization and promoting hepatocellular carcinoma growth.Functional & integrative genomics · 2026Article
- High expression of USP15 affects tumor progression and immune infiltration in hepatocellular carcinoma.Hepatology forum · 2026Article
50 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetastasis is a key feature of malignant tumors and significantly contributes to their high mortality, particularly in hepatocellular carcinoma (HCC). Therefore, it is imperative to explore the mechanism of tumor metastasis. Recently, tumor-associated macrophages (TAMs) have been demonstrated to promote tumor progression, while TAM-derived molecules involved in HCC metastasis warrant further investigation.
methodsTHP-1 was treated with IL-4 (Interleukin-4) and IL-13 (Interleukin-13) for M2 polarized macrophages. Exosomes derived from M2 macrophages were characterized. Then, HCC cells or human umbilical vein endothelial cells (HUVECs) were co-cultured with M2 macrophages or treated with M2 macrophage-secreted exosomes. Next, Transwell®, Scratch assay, tube formation, and endothelial permeability assays were performed. Moreover, RT-PCR, western blotting, immunofluorescence, and ELISA were used to assess mRNA and protein expression levels. Finally, the miRNA expression profiles of exosomes derived from M2 and M0 macrophages were analyzed.
resultsM2 macrophage infiltration was correlated with metastasis and a poor prognosis in HCC patients. M2-derived exosomes were absorbed by HCC and HUVEC cells and promoted the epithelial-mesenchymal transition (EMT), vascular permeability, and angiogenesis. Notably, MiR-23a-3p levels were significantly higher in M2-derived exosomes and hnRNPA1 mediated miR-23a-3p packaging into exosomes. Phosphatase and tensin homolog (PTEN) and tight junction protein 1 (TJP1) were the targets of miR-23a-3p, as confirmed by luciferase reporter assays. Lastly, HCC cells co-cultured with M2-derived exosomes secreted more GM-CSF, VEGF, G-CSF, MCP-1, and IL-4, which in turn further recruited M2 macrophages.
conclusionsOur findings suggest that M2 macrophage-derived miR-23a-3p enhances HCC metastasis by promoting EMT and angiogenesis, as well as increasing vascular permeability. Video Abstract.
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