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Characterization of Extracellular Vesicles Isolated from Plasma and Urine of Healthy Donors and Cancer Patients

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Submitted:

13 October 2016

Posted:

14 October 2016

Withdrawn:

16 December 2016

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Abstract
Extracellular vesicles (EVs) were detected and quantified in blood and urine of healthy donors and cancer patients using serial centrifugation protocols and high- resolution flow cytometry. EVs were phenotypically characterized by measuring exposure of phosphatidylserine (PS) and activities of FX and TFPI as well as functionally analyzed for tenase activity, ERK phosphorylation and tumor cell migration. Plasmatic and urinary EVs contained mainly microparticles (MPs), accompanied by low amounts of exosomes or apoptotic bodies. In contrast to plasmatic MPs, urinary MPs from healthy donors did not expose PS, which argues for endothelial cells of the urinary tract as a source. In cancer patients, however, we found urinary MPs presenting PS. Their amount correlated positively with albumin excretion. This suggests that the glomerular membrane is leaky for plasmatic MPs as well as albumin; thus in the urine of cancer patients the EVs presenting PS might be obtained from the plasma. Positive correlations between tenase activity, ERK phosphorylation and potency to induce tumor cell migration suggest that TF-presenting EVs form PAR- activating tenase complexes with FVII and FX, activate PAR-2, induce ERK phosphorylation and trigger tumor cell migration. Our results representing proof-of-principle suggest that further studies in defined cancers and stages are warranted.
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Subject: Medicine and Pharmacology  -   Oncology and Oncogenics
Copyright: This open access article is published under a Creative Commons CC BY 4.0 license, which permit the free download, distribution, and reuse, provided that the author and preprint are cited in any reuse.
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