Heparin blocks transfer of extracellular vesicles between donor and recipient cells

NA Atai, L Balaj, H van Veen, XO Breakefield… - Journal of neuro …, 2013 - Springer
NA Atai, L Balaj, H van Veen, XO Breakefield, PA Jarzyna, CJF Van Noorden, J Skog
Journal of neuro-oncology, 2013Springer
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 …
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.
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