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

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.