Extracellular vesicles derived from pancreatic cancer cells BXPC3 or breast cancer cells MCF7 induce a permanent procoagulant shift to endothelial cells

• Published in: Thrombosis research 2020-03, Vol.187, p.170-179
• Main Authors: Djedidi-Amrane, Rania, Rousseau, Aurélie, Larsen, Annette K, Elalamy, Ismail, Van Dreden, Patrick, Gerotziafas, Grigoris T
• Format: Article
• Language: English
• Subjects: Cancer associated thrombosis; Endothelial cells; Extracellular vesicles; Hematology, Oncology, and Palliative Medicine; Life Sciences; Thrombin generation; Tissue factor
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2019.09.003

AbstractThe endothelium could be a potential target of cancer cell derived extracellular vesicles (CaCe-dEV). We investigated in vitro the effect of CaCe-dEV on the hemostatic balance of endothelial cells. Extracellular vesicles released from pancreas adenocarcinoma cells (BXPC3) or human breast cancer cells (MCF7) were isolated by differential centrifugation. Human umbilical vein endothelial cells (HUVEC) were cultured for 72 h in the presence or absence of CaCe-dEV. Subsequently, they were washed and re-cultivated over three cycles to get daughter cell generations (DG) which were not exposed to CaCe-dEV. Thrombin generation of normal platelet poor plasma (PPP) added in wells carrying HUVEC was assessed by the Calibrated Automated Thrombogram®. Tissue factor activity (TFa) and procoagulant phospholipid clotting time were assessed. Some traces of TFa were displayed by non-exposed HUVEC (0.18 ± 0.03 pM) and their EVs (1.2 ± 1.0 pM). Non-exposed HUVEC did not induce any detectable thrombin generation. BXPC3-dEV displayed significantly higher TFa as compared to MCF7-dEV (45 ± 5 pM versus 4.6 ± 2.3pM respectively; p