Circulating blood extracellular vesicles as a tool to assess endothelial injury and chemotherapy toxicity in adjuvant cancer patients

Gil Bar-Sela; Idan Cohen; Adva Avisar; David Loven; Anat Aharon

doi:10.1371/journal.pone.0240994

Circulating blood extracellular vesicles as a tool to assess endothelial injury and chemotherapy toxicity in adjuvant cancer patients

Gil Bar-Sela, Idan Cohen, Adva Avisar, David Loven, Anat Aharon

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Extracellular vesicles (EVs) are subcellular membrane blebs that include exosomes and microparticles, which represent a potential source for cancer biomarker discovery. We assess EVs characteristics as a tool to evaluate the endothelial and anti-tumor treatment injury during adjuvant chemotherapy in breast (BC) and colon cancer (CC) patients. Blood samples were taken from 29 BC and 25 CC patients before and after chemotherapy, as well as from healthy control donors (HC). Circulating blood EVs were isolated and characterized by size/concentration, membrane antigens for cell origin, thrombogenicity, and protein content. We observed higher EVs concentration and particle size in CC patients after chemotherapy compared with HC. Higher levels of endothelial EVs (CD144-positive) and vascular endothelial growth factor receptor 1 (VEGFR1), apparently as an indication of endothelial dysfunction, were found in all cancer patients, regardless of a given treatment, compared to HC. Levels of EVs labeled CD62E, CD34+41-, the lymphocyte markers CD11+ and CD-14+, Annexin-V, and the coagulation proteins TF and TFPI, however, sometimes demonstrate significant differences between patients, although HC did not show significant differences between patients pre- and post-chemotherapy. Most importantly, increasing levels of EVs encapsulated Angiostatin were found in patients with CC, while chemotherapy treatment leads to its notable rise in circulating blood EVs. Our results demonstrate the potential of EVs encapsulated Angiostatin as a tool to evaluate endothelial damage during adjuvant chemotherapy in BC and CC patients.

Original language	English
Article number	e0240994
Journal	PLoS ONE
Volume	15
Issue number	10 October
DOIs	https://doi.org/10.1371/journal.pone.0240994
State	Published - Oct 2020
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2020 Bar-Sela et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding

This work was funded by the: Israel Science Foundation (ISF), grant No 1413/21, and Rappaport Family Institute Grant 2012-2014. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Funders	Funder number
Rappaport Family Institute	2012-2014
Israel Science Foundation	1413/21

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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abstract = "Extracellular vesicles (EVs) are subcellular membrane blebs that include exosomes and microparticles, which represent a potential source for cancer biomarker discovery. We assess EVs characteristics as a tool to evaluate the endothelial and anti-tumor treatment injury during adjuvant chemotherapy in breast (BC) and colon cancer (CC) patients. Blood samples were taken from 29 BC and 25 CC patients before and after chemotherapy, as well as from healthy control donors (HC). Circulating blood EVs were isolated and characterized by size/concentration, membrane antigens for cell origin, thrombogenicity, and protein content. We observed higher EVs concentration and particle size in CC patients after chemotherapy compared with HC. Higher levels of endothelial EVs (CD144-positive) and vascular endothelial growth factor receptor 1 (VEGFR1), apparently as an indication of endothelial dysfunction, were found in all cancer patients, regardless of a given treatment, compared to HC. Levels of EVs labeled CD62E, CD34+41-, the lymphocyte markers CD11+ and CD-14+, Annexin-V, and the coagulation proteins TF and TFPI, however, sometimes demonstrate significant differences between patients, although HC did not show significant differences between patients pre- and post-chemotherapy. Most importantly, increasing levels of EVs encapsulated Angiostatin were found in patients with CC, while chemotherapy treatment leads to its notable rise in circulating blood EVs. Our results demonstrate the potential of EVs encapsulated Angiostatin as a tool to evaluate endothelial damage during adjuvant chemotherapy in BC and CC patients.",

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Circulating blood extracellular vesicles as a tool to assess endothelial injury and chemotherapy toxicity in adjuvant cancer patients

Abstract

Bibliographical note

Funding

UN SDGs

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