Cancer Cell-Derived Extracellular Vesicles Are Associated with Coagulopathy Causing Ischemic Stroke via Tissue Factor-Independent Way: The OASIS-CANCER Study

• Published in: PloS one Vol. 11; no. 7; p. e0159170
• Main Authors: Bang, Oh Young, Chung, Jong-Won, Lee, Mi Ji, Kim, Suk Jae, Cho, Yeon Hee, Kim, Gyeong-Moon, Chung, Chin-Sang, Lee, Kwang Ho, Ahn, Myung-Ju, Moon, Gyeong Joon
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.07.2016; Public Library of Science (PLoS)
• Subjects: Aged; Biology and Life Sciences; Biomedical research; Brain cancer; Cancer; Cell adhesion; Cell adhesion molecules; Complications and side effects; Correlation analysis; Cytometry; Disease; Disseminated Intravascular Coagulation - blood; Disseminated Intravascular Coagulation - etiology; Disseminated Intravascular Coagulation - pathology; Endothelial cells; Epithelial cells; Extracellular vesicles; Extracellular Vesicles - pathology; Female; Fibrin Fibrinogen Degradation Products - analysis; Flow cytometry; Geriatrics; Health risk assessment; Humans; Ischemia; Laboratories; Male; Medical research; Medicine; Medicine and Health Sciences; Metastasis; MicroRNAs; Middle Aged; Neoplasms - blood; Neoplasms - complications; Neoplasms - pathology; Neurology; NMR; Nuclear magnetic resonance; Older people; Oncology; Patients; Platelets; Research and Analysis Methods; Risk factors; Serum levels; Stem cells; Stroke; Stroke - blood; Stroke - etiology; Stroke - pathology; Studies; Thromboembolism; Thromboplastin - analysis; Thrombosis; Tissue factor; Vesicles; South Korea
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0159170

Cancer and stroke, which are known to be associated with one another, are the most common causes of death in the elderly. However, the pathomechanisms that lead to stroke in cancer patients are not well known. Circulating extracellular vesicles (EVs) play a role in cancer-associated thrombosis and tumor progression. Therefore, we hypothesized that cancer cell-derived EVs cause cancer-related coagulopathy resulting in ischemic stroke. Serum levels of D-dimer and EVs expressing markers for cancer cells (epithelial cell adhesion molecule [CD326]), tissue factor (TF [CD142]), endothelial cells (CD31+CD42b-), and platelets (CD62P) were measured using flow cytometry in (a) 155 patients with ischemic stroke and active cancer (116 - cancer-related, 39 - conventional stroke mechanisms), (b) 25 patients with ischemic stroke without cancer, (c) 32 cancer patients without stroke, and (d) 101 healthy subjects. The levels of cancer cell-derived EVs correlated with the levels of D-dimer and TF+ EVs. The levels of cancer cell-derived EVs (CD326+ and CD326+CD142+) were higher in cancer-related stroke than in other groups (P<0.05 in all the cases). Path analysis showed that cancer cell-derived EVs are related to stroke via coagulopathy as measured by D-dimer levels. Poor correlation was observed between TF+ EV and D-dimer, and path analysis demonstrated that cancer cell-derived EVs may cause cancer-related coagulopathy independent of the levels of TF+ EVs. Our findings suggest that cancer cell-derived EVs mediate coagulopathy resulting in ischemic stroke via TF-independent mechanisms.