ArticleThe Journal of biological chemistry2016
Fibronectin on the Surface of Myeloma Cell-derived Exosomes Mediates Exosome-Cell Interactions.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
192 citing papers in PubMed, 295 citations in OpenAlex.
- Role of Extracellular Vesicles in Shaping Immune Responses in the Lymph Node Microenvironment.Biology of the cell · 2026Review
- Size-Based Proteomic Signatures of Extracellular Vesicles Derived from Umbilical Cord Mesenchymal Stem Cells Fractionated by EXODUS.International journal of molecular sciences · 2026Article
- The 'sugar' side of extracellular vesicle-glycome: a panorama from basic characteristics, deciphering technologies, functions, to applications.Journal of nanobiotechnology · 2026Review
- Biology and therapeutic potential of extracellular vesicle targeting and uptake.Nature reviews. Molecular cell biology · 2026Review
- Barrier breakdown: lung-brain crosstalk in systemic inflammation.Journal of neuroinflammation · 2026Review
- Redefining long-acting injectables: the emerging role of extracellular vesicles in sustained drug delivery.Drug delivery and translational research · 2026Review
- Tumor exosomes impact functional hallmarks of cancer.Cancer metastasis reviews · 2026Review
- Extracellular matrix polysaccharides and glycoproteins in ovarian cancer: structural-functional macromolecular perspectives and potential exosome-derived biomarkers.Cell communication and signaling : CCS · 2026Review
- Apoptotic extracellular vesicles: unveiling mechanisms, diverse functions, and biomedical implications.Apoptosis : an international journal on programmed cell death · 2026Review
- Does extracellular vesicle specificity truly exist?Cell communication and signaling : CCS · 2026Review
- The interplay between the extracellular matrix and extracellular vesicle-associated microRNAs.Cell communication and signaling : CCS · 2026Review
- Uncovering the dynamics of extracellular vesicle microRNA trafficking in multiple sclerosis: delivery, diversion and retention.Extracellular vesicles and circulating nucleic acids · 2026Review
- Understanding hairy cell leukemia in the context of mature B-cell neoplasms: tumor microenvironment and extracellular vesicle contribution to disease pathogenesis.Frontiers in immunology · 2026Review
- Intranasal delivery of DPSC-derived small extracellular vesicles-encased phloroglucinol attenuates non-motor and motor deficits and promotes neurogenesis in an in vivo rat model of Parkinson's disease.Stem cell research & therapy · 2025Article
- Extracellular vesicle bioactivity and potential for clinical development are determined by mesenchymal stromal cell clonal subtype.Stem cell research & therapy · 2025Article
- New insights into extracellular vesicles in metastatic cancer: From mechanisms to diagnostics and targeted therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- SDC2 and FN as cargo proteins in circulating extracellular vesicles in obese breast cancer patients with lymph node metastasis.Scientific reports · 2025Article
- Potential of Exosomes as Multifunctional Nanocarriers for Targeted Drug Delivery.Molecular biotechnology · 2025Review
- Whole-genome methylation profiling of extracellular vesicle DNA in gastric cancer identifies intercellular communication features.Nature communications · 2025Article
- Extracellular Vesicles in Osteogenesis: A Comprehensive Review of Mechanisms and Therapeutic Potential for Bone Regeneration.Current issues in molecular biology · 2025Review
132 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Exosomes regulate cell behavior by binding to and delivering their cargo to target cells; however, the mechanisms mediating exosome-cell interactions are poorly understood. Heparan sulfates on target cell surfaces can act as receptors for exosome uptake, but the ligand for heparan sulfate on exosomes has not been identified. Using exosomes isolated from myeloma cell lines and from myeloma patients, we identify exosomal fibronectin as a key heparan sulfate-binding ligand and mediator of exosome-cell interactions. We discovered that heparan sulfate plays a dual role in exosome-cell interaction; heparan sulfate on exosomes captures fibronectin, and on target cells it acts as a receptor for fibronectin. Removal of heparan sulfate from the exosome surface releases fibronectin and dramatically inhibits exosome-target cell interaction. Antibody specific for the Hep-II heparin-binding domain of fibronectin blocks exosome interaction with tumor cells or with marrow stromal cells. Regarding exosome function, fibronectin-mediated binding of exosomes to myeloma cells activated p38 and pERK signaling and expression of downstream target genes DKK1 and MMP-9, two molecules that promote myeloma progression. Antibody against fibronectin inhibited the ability of myeloma-derived exosomes to stimulate endothelial cell invasion. Heparin or heparin mimetics including Roneparstat, a modified heparin in phase I trials in myeloma patients, significantly inhibited exosome-cell interactions. These studies provide the first evidence that fibronectin binding to heparan sulfate mediates exosome-cell interactions, revealing a fundamental mechanism important for exosome-mediated cross-talk within tumor microenvironments. Moreover, these results imply that therapeutic disruption of fibronectin-heparan sulfate interactions will negatively impact myeloma tumor growth and progression.
Indexed as
Identifiers
What OpenQuestion holds
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.