title: Heparin blocks transfer of extracellular vesicles between donor and recipient cells.
abstract: Extracellular vesicles (EVs) have been implicated in tumorigenesis. Biomolecules which can block EV binding and uptake into recipient cells may be of therapeutic value as well as enhance understanding of EV biology. Here, we show that heparin interacts with uptake of tumor-derived as well as non-tumor-derived EVs into recipient cells. Incubation of glioma cell-derived EVs with heparin resulted in micron-sized structures observed by transmission electron microscopy, with EVs clearly visible within these structures. Inclusion of heparin greatly diminished transfer of labeled EVs from donor to recipient tumor cells. We also show a direct interaction between heparin and EVs using confocal microscopy. We found that the block in EV uptake was at the level of cell binding and not internalization. Finally, incubation of glioma-derived EVs containing EGFRvIII mRNA with heparin reduced transfer of this message to recipient cells. The effect of heparin on EVs uptake may provide a unique tool to study EV function. It may also foster research of heparin or its derivatives as a therapeutic for disease in which EVs play a role.
authors.affiliation: Department of Neurology and Program in Neuroscience, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
authors.forename: Nadia A
authors.initials: NA
authors.lastname: Atai
authors.forename: Leonora
authors.initials: L
authors.lastname: Balaj
authors.forename: Henk
authors.initials: H
authors.lastname: van Veen
authors.forename: Xandra O
authors.initials: XO
authors.lastname: Breakefield
authors.forename: Peter A
authors.initials: PA
authors.lastname: Jarzyna
authors.forename: Cornelis J F
authors.initials: CJ
authors.lastname: Van Noorden
authors.forename: Johan
authors.initials: J
authors.lastname: Skog
authors.forename: Casey A
authors.initials: CA
authors.lastname: Maguire
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects*; D005434:Flow Cytometry; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D022161:Transport Vesicles / Q000187:drug effects*; D014407:Tumor Cells, Cultured
chemical_list: D000925:Anticoagulants; D012333:RNA, Messenger; C410723:epidermal growth factor receptor VIII; D006493:Heparin; D066246:ErbB Receptors