ArticleCell death & disease2019
Exosomes from CD99-deprived Ewing sarcoma cells reverse tumor malignancy by inhibiting cell migration and promoting neural differentiation.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Extracellular vesicles modulate integrin signaling and subcellular energetics to promote pulmonary lymphangioleiomyomatosis metastasis.Communications biology · 2025Article
- Small Extracellular Vesicles as Biomarkers in Sarcoma Follow-Up: Protocol for a Prospective, Multicentric Pilot Study.JMIR research protocols · 2025Article
- The therapeutic potential of exosomes in bone cancers: osteosarcoma, chondrosarcoma, and Ewing sarcoma.Investigational new drugs · 2025Review
- The Double Life of microRNAs in Bone Sarcomas: Oncogenic Drivers and Tumor Suppressors.International journal of molecular sciences · 2025Review
- Microvesicles Derived from Human Bronchial Epithelial Cells Regulate Macrophage Activation DuringJournal of proteome research · 2025Article
- Exploration of research hotspots and evolutionary trends in osteosarcoma pulmonary metastasis: A comprehensive bibliometric analysis spanning five decades.Journal of orthopaedics · 2025Article
- CD99: A Key Regulator in Immune Response and Tumor Microenvironment.Biomolecules · 2025Review
- Role of exosomes in diagnosis, prognostication, and treatment of pediatric solid tumors.Molecular therapy. Oncology · 2025Review
- Extracellular Vesicles in Sarcoma: Implications for Tumor Progression and Therapy.International journal of nanomedicine · 2025Review
- Identification of ENO-1 positive extracellular vesicles as a circulating biomarker for monitoring of Ewing sarcoma.Cancer science · 2024Article
- Stemness and Cell Cycle Regulators and Their Modulation by Retinoic Acid in Ewing Sarcoma.Current issues in molecular biology · 2024Article
- CD99 Modulates the Proteomic Landscape of Ewing Sarcoma Cells and Related Extracellular Vesicles.International journal of molecular sciences · 2024Article
- Ewing sarcoma treatment: a gene therapy approach.Cancer gene therapy · 2023Review
- Exosome-Based Liquid Biopsy Approaches in Bone and Soft Tissue Sarcomas: Review of the Literature, Prospectives, and Hopes for Clinical Application.International journal of molecular sciences · 2023Review
- Functions and therapeutic potentials of exosomes in osteosarcoma.Acta materia medica · 2022Article
- Novel Targeted Therapeutic Strategies for Ewing Sarcoma.Cancers · 2022Review
- miR-214-3p Is Commonly Downregulated by EWS-FLI1 and by CD99 and Its Restoration Limits Ewing Sarcoma Aggressiveness.Cancers · 2022Article
- Cancer-Derived Extracellular Vesicles: Their Role in Sarcoma.Life (Basel, Switzerland) · 2022Review
- Review
- The basic characteristics of extracellular vesicles and their potential application in bone sarcomas.Journal of nanobiotechnology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ewing sarcoma (EWS) is an aggressive mesenchymal tumor with unmet clinical need and significant social impacts on children, adolescents, and young adults. CD99, a hallmark surface molecule of EWS, participates in crucial biological processes including cell migration, differentiation, and death. EWS cells can release CD99 through exosomes (EXOs), specialized extracellular vesicles with major cell communication roles. Here we show that, as a consequence of CD99 silencing, EWS cells deliver exosomes with oncosuppressive functions that significantly reduce tumor aggressiveness. These CD99-lacking microvesicles modulate gene expression of the EWS-recipient cells, reduce proliferation and migration, in turn inducing a more-differentiated less-malignant phenotype. The most relevant effects were detected on the activator protein-1 signaling pathway whose regulation was found to be dependent on the specific cargo loaded in vesicles after CD99 shutdown. Investigation of the miRNA content of CD99-deprived EXOs identified miR-199a-3p as a key driver able to reverse EWS malignancy in experimental models as well as in clinical specimens. All together, our data provide evidence that the abrogation of CD99 in EWS tumor cells leads to produce and release EXOs capable to transfer their antineoplastic effects into the nearby tumor cells, suggesting a novel atypical role for these microvesicles in reversion of malignancy rather than in priming the soil for progression and metastatic seeding. This conceptually innovative approach might offer a new therapeutic opportunity to treat a tumor still refractory to most treatments.
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Registered trials
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.