ArticleJournal of experimental & clinical cancer research : CR2019
Macrophages derived exosomes deliver miR-223 to epithelial ovarian cancer cells to elicit a chemoresistant phenotype.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 231 papers, 2 of them syntheses that pooled it.
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Who cites it
231 citing papers in PubMed, 2 syntheses or guidelines pooled it, 385 citations in OpenAlex.
- Unraveling the role of M2 TAMs in ovarian cancer dynamics: a systematic review.Journal of translational medicine · 2025Pooled it
- The current trend of exosome in epithelial ovarian cancer studies: A bibliometric review.Frontiers in pharmacology · 2023Pooled it
- Potential Role of Exosomes in the Pathogenesis, Diagnosis, and Treatment of Ovarian Cancer.Cancers · 2026Review
- The updated role of exosomes in cancer diagnosis and therapy.Discover oncology · 2026Review
- TAMs in the Gynecological Tumor Microenvironment: Insights from Cross-Cancer Studies for Immunotherapy.Cancers · 2026Review
- Empowering women's health with miRNA-integrated nanochemical approaches: from reproductive health to cancer care.RSC advances · 2026Review
- Klebsiella pneumoniae LPS drives stromal-mediated repression of p53 and colorectal cancer chemoresistance.Cell death & disease · 2026Article
- The role of small extracellular vesicles in ovarian cancer drug resistance: from bench clues to clinical implications.Journal of ovarian research · 2026Review
- Exosomes in oncofertility: emerging roles in chemotherapy-induced reproductive damage and fertility preservation.Reproduction & fertility · 2026Review
- RNA Regulatory Networks: Key Hubs in the Panorama of Cancer and Emerging Therapeutic Targets.MedComm · 2026Review
- Polarization-Specific Macrophage-Derived Extracellular Vesicles: Molecular Cargo, Tumor Microenvironment Remodeling, and Therapeutic Opportunities.International journal of nanomedicine · 2026Review
- Exosomes in Ovarian Cancer: Promoters, Biomarkers, and Therapeutic Targets.International journal of nanomedicine · 2026Review
- Role of the tumor microenvironment in chemotherapy resistance in ovarian cancer and targeted therapy.Journal of ovarian research · 2025Review
- Advances in the use of exosomes for the diagnosis and treatment of ovarian cancer.World journal of surgical oncology · 2025Review
- Insights into spheroid formation: interaction of ovarian cancer cells with macrophage populations in the tumor microenvironment.Journal of translational medicine · 2025Article
- Hypoxia-induced exosomal LUCAT1 promotes osimertinib resistance in lung adenocarcinoma by stabilizing c-MET.Cell death & disease · 2025Article
- Polarized Macrophages and Their Exosomes: Implications for Autoimmune and Immune-Mediated Diseases.Biology · 2025Review
- Signaling networks and MiRNA crosstalk in ovarian cancer chemoresistance.Journal of ovarian research · 2025Review
- Cell-free and extracellular vesicle microRNAs with clinical utility for solid tumors.Molecular oncology · 2025Review
- Exosomes in ovarian cancer: Impact on drug resistance and advances in SERS detection techniques.Journal of pharmaceutical analysis · 2025Review
171 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHow exosomal microRNAs (miRNAs) derived from macrophages contribute to the development of drug resistance in the context of the hypoxic tumor microenvironment in epithelial ovarian cancer (EOC) remains poorly understood.
methodsThe miRNA levels were detected by qRT-PCR. Protein levels of HIF-1α, CD163 and PTEN-PI3K/AKT pathway were assessed by Western blot (WB) and Immunohistochemistry (IHC). Exosomes were isolated, and then confirmed by Transmission electron microscopy (TEM), Nanoparticle Tracking Analysis (NTA) and WB. Internalization of macrophages-secreted exosomes in EOC cells was detected by Confocal microscope. Subsequently, Dual-luciferase reporter assay verified PTEN was the target of miR-223. Gain- and loss-of-function experiments, rescue experiments, and SKOV3 xenograft models were performed to uncover the underlying mechanisms of miR-223 and PTEN-PI3K/AKT pathway, as well as the exosomal miR-223 in inducing multidrug resistance in vitro and in vivo.
resultsHere, we showed hypoxic EOC cells triggered macrophages recruitment and induced macrophages into a tumor-associated macrophage (TAM)-like phenotype; exosomes derived from hypoxic macrophages enhanced the malignant phenotype of EOC cells, miR-223 was enriched in exosomes released from macrophages under hypoxia, which could be transferred to the co-cultivated EOC cells, accompanied by enhanced drug resistant of EOC cells. Besides, results from a functional assay revealed that exosomal miR-223 derived from macrophages promoted the drug resistance of EOC cells via the PTEN-PI3K/AKT pathway both in vivo and in vitro. Furthermore, patients with high HIF-1a expression had statistically higher CD163+ cell infiltration and intertumoral levels of miR-223. Finally, circulating exosomal miR-223 levels were closely related to the recurrence of EOC.
conclusionsThese data indicate a unique role of exosomal miR-223 in the cross-talk between macrophages and EOC cells in chemotherapy resistance, through a novel exosomal miR-223/PTEN-PI3K/AKT signaling pathway.
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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.