TY - JOUR
T1 - What is the blood concentration of extracellular vesicles?
T2 - Implications for the use of extracellular vesicles as blood-borne biomarkers of cancer
AU - Johnsen, Kasper Bendix
AU - Gudbergsson, Johann Mar
AU - Andresen, Thomas Lars
AU - Simonsen, Jens Bæk
N1 - Copyright © 2018 Elsevier B.V. All rights reserved.
PY - 2019/1
Y1 - 2019/1
N2 - Circulating biomarkers have a great potential in diagnosing cancer diseases at early stages, where curative treatment is a realistic possibility. In the recent years, using extracellular vesicles (EVs) derived from blood as biomarkers has gained widespread popularity, mainly because they are thought to be easy to isolate and carry a vast variety of biological cargos that can be analyzed for biomarker purposes. However, our current knowledge on the plasma EV concentration in normophysiological states is sparse. Here, we provide the very first mean estimate of the plasma EV concentration based on values obtained from a thorough literature review. The different estimates obtained from the literature are correlated to the isolation techniques used to obtain them, illustrating how some methodologies may over- or underestimate the plasma EV concentration. We also show that the estimated plasma EV concentration (approximately 1010 EVs per mL) defines EVs as a minority population compared to other colloidal particles of the systemic circulation, namely the lipoproteins, which are known contaminants in EV isolates and carry biomarker molecules themselves. Lastly, we introduce the possibility of regarding EVs and lipoproteins as a continuum of lipid-containing particles to which biomarker molecules can be associated. Using such a holistic approach, increased strength of plasma-derived cancer biomarkers may soon be revealed.
AB - Circulating biomarkers have a great potential in diagnosing cancer diseases at early stages, where curative treatment is a realistic possibility. In the recent years, using extracellular vesicles (EVs) derived from blood as biomarkers has gained widespread popularity, mainly because they are thought to be easy to isolate and carry a vast variety of biological cargos that can be analyzed for biomarker purposes. However, our current knowledge on the plasma EV concentration in normophysiological states is sparse. Here, we provide the very first mean estimate of the plasma EV concentration based on values obtained from a thorough literature review. The different estimates obtained from the literature are correlated to the isolation techniques used to obtain them, illustrating how some methodologies may over- or underestimate the plasma EV concentration. We also show that the estimated plasma EV concentration (approximately 1010 EVs per mL) defines EVs as a minority population compared to other colloidal particles of the systemic circulation, namely the lipoproteins, which are known contaminants in EV isolates and carry biomarker molecules themselves. Lastly, we introduce the possibility of regarding EVs and lipoproteins as a continuum of lipid-containing particles to which biomarker molecules can be associated. Using such a holistic approach, increased strength of plasma-derived cancer biomarkers may soon be revealed.
UR - http://www.scopus.com/inward/record.url?scp=85058224689&partnerID=8YFLogxK
U2 - 10.1016/j.bbcan.2018.11.006
DO - 10.1016/j.bbcan.2018.11.006
M3 - Review article
C2 - 30528756
SN - 0304-419X
VL - 1871
SP - 109
EP - 116
JO - B B A - Reviews on Cancer
JF - B B A - Reviews on Cancer
IS - 1
ER -