ArticleHaematologica2022
Extracellular vesicles mediate the communication between multiple myeloma and bone marrow microenvironment in a NOTCH dependent way.
Article in Haematologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Mitochondrial Communication Networks in the Bone Microenvironment: From the Maintenance of Homeostasis to Translational Interventions for Bone Diseases.Stem cell reviews and reports · 2026Review
- Jagged-dependent Notch signaling governs extracellular vesicle bioactivity in multiple myeloma.Leukemia · 2026Article
- Surface Proteomics of Cancer-Derived Extracellular Vesicles Reveals Universal Heat Shock Proteins and Cancer Signatures.Molecular & cellular proteomics : MCP · 2026Article
- Article
- Continuous multi-omics pathway enrichment analysis resolves hidden functional heterogeneity.Briefings in bioinformatics · 2026Article
- Proteasomal inhibition compromises microvascular integrity via distinct effects on non-immune endothelial cells and immune cells.Frontiers in immunology · 2026Article
- Extracellular vesicles in multiple myeloma-bone marrow niche crosstalk: from cellular dialogue to clinical perspectives.Journal of translational medicine · 2025Review
- Ischemic stroke and intervention strategies based on the timeline of stroke progression: Review and prospects.Acta pharmaceutica Sinica. B · 2025Review
- Examining the contribution of Notch signaling to lung disease development.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Review
- ActivinA modulates B-acute lymphoblastic leukaemia cell communication and survival by inducing extracellular vesicles production.Scientific reports · 2024Article
- Review
- Hitting the target: cell signaling pathways modulation by extracellular vesicles.Extracellular vesicles and circulating nucleic acids · 2024Review
- The Potential of JAG Ligands as Therapeutic Targets and Predictive Biomarkers in Multiple Myeloma.International journal of molecular sciences · 2023Article
- Metastatic Dissemination: Role of Tumor-Derived Extracellular Vesicles and Their Use as Clinical Biomarkers.International journal of molecular sciences · 2023Review
- Non-Classical Intercellular Communications: Basic Mechanisms and Roles in Biology and Medicine.International journal of molecular sciences · 2023Review
- Extracellular vesicles in hematological malignancies: EV-dence for reshaping the tumoral microenvironment.Frontiers in immunology · 2023Review
- Current Status of Research on Small Extracellular Vesicles for the Diagnosis and Treatment of Urological Tumors.Cancers · 2022Review
- Cancer Three-Dimensional Spheroids Mimic In Vivo Tumor Features, Displaying "Inner" Extracellular Vesicles and Vasculogenic Mimicry.International journal of molecular sciences · 2022Article
- Role of Notch2 pathway in mature B cell malignancies.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple myeloma (MM) is an incurable hematologic neoplasm, whose poor prognosis is deeply affected by the propensity of tumor cells to localize in the bone marrow (BM) and induce the protumorigenic activity of normal BM cells, leading to events associated with tumor progression, including tumor angiogenesis, osteoclastogenesis, and the spread of osteolytic bone lesions. The interplay between MM cells and the BM niche does not only rely on direct cell-cell interaction, but a crucial role is also played by MM-derived extracellular vesicles (MM-EV). Here, we demonstrated that the oncogenic NOTCH receptors are part of MM-EV cargo and play a key role in EV protumorigenic ability. We used in vitro and in vivo models to investigate the role of EV-derived NOTCH2 in stimulating the protumorigenic behavior of endothelial cells and osteoclast progenitors. Importantly, MM-EV can transfer NOTCH2 between distant cells and increase NOTCH signaling in target cells. MM-EV stimulation increases endothelial cell angiogenic ability and osteoclast differentiation in a NOTCH2-dependent way. Indeed, interfering with NOTCH2 expression in MM cells may decrease the amount of NOTCH2 also in MM-EV and affect their angiogenic and osteoclastogenic potential. Finally, we demonstrated that the pharmacologic blockade of NOTCH activation by γ-secretase inhibitors may hamper the biological effect of EV derived by MM cell lines and by the BM of MM patients. These results provide the first evidence that targeting the NOTCH pathway may be a valid therapeutic strategy to hamper the protumorigenic role of EV in MM as well as other tumors.
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