Commonly used drugs function through extracellular vesicles

Extracellular vesicles (EVs) are attractive candidates for biomarker research, because their content reflects the parental cell status. Researchers from the University Medical Center Utrecht examined whether tumor cell derived EVs mirrored the cellular changes caused by treatment with cetuximab, a therapeutic antibody that blocks activation of EGF receptor (EGFR)1. They found that EV levels of EGFR and phospho-EGFR were reduced after cetuximab treatment, reflecting similar changes in the parental cells. In addition, cetuximab was found associated with EVs. They suggest that EVs could serve as biomarkers to monitor cetuximab treatment. Association of cetuximab with EVs might influence its behavior.

Researchers from the University of Edinburg investigated the potential hormonal regulation of ECV transfer and report that desmopressin, a vasopressin analogue, stimulated the uptake of fluorescently loaded ECVs into a kidney collecting duct cell line (mCCDC11) and into primary cells2. Exposure of mCCDC11cells to ECVs isolated from cells overexpressing microRNA-503 led to downregulated expression of microRNA-503 target genes, but only in the presence of desmopressin. Furthermore, in a patient with central diabetes insipidus, desmopressin reduced the excretion of ECVs derived from glomerular and proximal tubular cells. These data are consistent with vasopressin-regulated uptake of ECVs. The researchers suggest that therapeutically, ECVs may be a vehicle by which RNA therapy could be targeted to specific cells for the treatment of kidney disease.

  1. van Dommelen SM, van der Meel R van Solinge WW, Coimbra M, Vader P, Schiffelers RM. (2016) Cetuximab treatment alters the content of extracellular vesicles released from tumor cells. Nanomedicine (Lond) 11(8):881-90. [abstract]
  2. Oosthuyzen W, Scullion KM, Ivy JR, Morrison EE, Hunter RW, Starkey Lewis PJ, O’Duibhir E, Street JM, Caporali A, Gregory CD, Forbes SJ, Webb DJ, Bailey MA, Dear JW. (2016) Vasopressin Regulates Extracellular Vesicle Uptake by Kidney Collecting Duct Cells. J Am Soc Nephrol [Epub ahead of print]. [abstract]

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