title: Cancer Cell-Derived Extracellular Vesicles Are Associated with Coagulopathy Causing Ischemic Stroke via Tissue Factor-Independent Way: The OASIS-CANCER Study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our findings suggest that cancer cell-derived EVs mediate coagulopathy resulting in ischemic stroke via TF-independent mechanisms.
authors.affiliation: Departments of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Translational and Stem Cell Research Laboratory on Stroke, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Oh Young
authors.initials: OY
authors.lastname: Bang
authors.affiliation: Departments of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Translational and Stem Cell Research Laboratory on Stroke, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Chung
authors.affiliation: Departments of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Mi Ji
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Departments of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Suk Jae
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Translational and Stem Cell Research Laboratory on Stroke, Samsung Medical Center, Seoul, Republic of Korea.|Clinical Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea.
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Cho
authors.affiliation: Departments of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Gyeong-Moon
authors.initials: GM
authors.lastname: Kim
authors.affiliation: Departments of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Chin-Sang
authors.initials: CS
authors.lastname: Chung
authors.affiliation: Departments of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Departments of Hemato-oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Myung-Ju
authors.initials: MJ
authors.lastname: Ahn
authors.affiliation: Translational and Stem Cell Research Laboratory on Stroke, Samsung Medical Center, Seoul, Republic of Korea.|Clinical Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea.
authors.forename: Gyeong Joon
authors.initials: GJ
authors.lastname: Moon
mesh_terms: D000368:Aged; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000209:etiology* / Q000473:pathology; D000067128:Extracellular Vesicles / Q000473:pathology*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000150:complications* / Q000473:pathology; D020521:Stroke / Q000097:blood / Q000209:etiology* / Q000473:pathology; D013925:Thromboplastin / Q000032:analysis*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D013925:Thromboplastin