ArticleInternational journal of biological sciences2024
Hypoxic tumor-derived exosomal miR-4488 induces macrophage M2 polarization to promote liver metastasis of pancreatic neuroendocrine neoplasm through RTN3/FABP5 mediated fatty acid oxidation.
Article in International journal of biological sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Thyroid cancer-derived exosomal SPP1 promotes tumor progression by driving macrophage M2 polarization through the CD44/JAK2/STAT3 signaling pathway.Organogenesis · 2026Article
- mTORC2 regulates lipid metabolism-driven TAMs via the PPAR-γ/CD36 pathway to promote liposarcoma progression.Adipocyte · 2026Article
- Fatty Acid-Binding Protein 5 Potentially Regulates the Proliferation and Metastasis of Uveal Melanoma Cells Through the PI3K/AKT/mTOR Signaling Pathway.CNS neuroscience & therapeutics · 2026Article
- Long-term survival and molecular heterogeneity of sporadic multifocal non-functional pancreatic neuroendocrine tumors.iScience · 2026Article
- Tumor-Associated Macrophage Exosomal miR-142-5p Drives Prostate Cancer Neuroendocrine Differentiation via RERG/Ras/ERK Axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Exosome-mediated hepatocellular carcinoma progression by modulating macrophage metabolic reprogramming and macrophage M2 polarization via exosome-derived hsa_circ_0057320-miR-28-5p/E2F6 axis.Journal of translational medicine · 2026Article
- Single-Cell and Spatial Transcriptomics Reframe the Immunosuppressive Microenvironment of Neuroendocrine Neoplasms.Cancers · 2026Review
- Extracellular vesicles in solid tumors: from tumor ecology to engineered therapeutics.Molecular cancer · 2026Review
- Understanding how hypoxia contributes to liver cancer stem cells maintenance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Hypoxia‑induced exosomal CAMTA1 promotes radio‑resistance in MDA‑MB‑231 cells by regulating NRG1 to mediate M2 macrophage polarization.International journal of oncology · 2026Article
- Potential role of leptin in colorectal cancer liver metastasis involving lipid metabolic reprogramming and immunosuppressive macrophage polarization.Scientific reports · 2026Article
- Non-coding RNAs: modulators of signaling pathways and prognostic biomarkers in digestive system cancer.Molecular cancer · 2026Review
- Article
- Tissue-Based Transcriptomic Profiling of Gastrointestinal Graft Versus Host Disease Reveals Immune and MicroRNA Dysregulation.International journal of molecular sciences · 2026Article
- Contribution of tumor-derived extracellular vesicles in the establishment of the pre-metastatic niche: lessons learned from past experimentations and future directions.Clinical & experimental metastasis · 2026Review
- Immunosuppressive Environment of Pancreatic NENs-A Review.Biomedicines · 2026Review
- TGFBI deficiency facilitates tumor associated macrophages M2 polarization and angiogenesis to promote pancreatic neuroendocrine neoplasms progression.Cancer cell international · 2026Article
- Tumor-associated macrophages: potential therapeutic strategies and future prospects in radioresistance of cancer.Frontiers in immunology · 2026Review
- Advances in understanding exosome-mediated regulation of macrophage function.Frontiers in immunology · 2026Review
- Macrophage-linked lipid metabolic signatures for HCC prognosis identified through integrated bulk and single-cell transcriptomics.Frontiers in immunology · 2026Article
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Authors and funding
15 authors.
Funding
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Abstract
Tumor-associated macrophages (TAMs) represent a predominant cellular component within the tumor microenvironment (TME) of pancreatic neuroendocrine neoplasms (pNENs). There is a growing body of evidence highlighting the critical role of exosomes in facilitating communication between tumor cells and TAMs, thereby contributing to the establishment of the premetastatic niche. Nonetheless, the specific mechanisms through which exosomes derived from tumor cells influence macrophage polarization under hypoxic conditions in pNENs, and the manner in which these interactions support cancer metastasis, remain largely unexplored. Recognizing the capacity of exosomes to transfer miRNAs that can modify cellular behaviors, our research identified a significant overexpression of miR-4488 in exosomes derived from hypoxic pNEN cells. Furthermore, we observed that macrophages that absorbed circulating exosomal miR-4488 underwent M2-like polarization. Our investigations revealed that miR-4488 promotes M2-like polarization by directly targeting and suppressing RTN3 in macrophages. This suppression of RTN3 enhances fatty acid oxidation and activates the PI3K/AKT/mTOR signaling pathway through the interaction and downregulation of FABP5. Additionally, M2 polarized macrophages contribute to the formation of the premetastatic niche and advance pNENs metastasis by releasing MMP2, thereby establishing a positive feedback loop involving miR-4488, RTN3, FABP5, and MMP2 in pNEN cells. Together, these findings shed light on the role of exosomal miRNAs from hypoxic pNEN cells in mediating interactions between pNEN cells and intrahepatic macrophages, suggesting that miR-4488 holds potential as a valuable biomarker and therapeutic target for pNENs.
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