title: Pancreatic Cancer-Induced Neutrophil Extracellular Traps: A Potential Contributor to Cancer-Associated Thrombosis.
abstract: Pancreatic cancer (PaCa) is a highly metastatic cancer, and patients are at high risk of developing venous thromboembolism (VTE). Neutrophil extracellular traps (NETs) have been associated with cancer metastasis and cancer-associated thrombosis, but the ability of cancer to stimulate NET release is not known. The release of NETs has been shown to be a slow process and requires reactive oxygen species (ROS) production. Studies suggest that activated platelets are important mediators in the release. Here, we show that PaCa cells can stimulate the rapid release of NETs, independently of ROS production. We further assessed the role of platelets in PaCa-induced NETs and observed a trend of increased the NET release by PaCa-primed platelets. Additionally, NETs promoted thrombus formation under venous shear stress ex vivo. Taken together, our results suggest that PaCa-induced NETs can contribute to the high risk of venous thromboembolism development in PaCa patients, and reveal NETs as a potential therapeutic target.
authors.affiliation: School of Biomedical Sciences, Curtin University, 6102 Perth, Australia. n.abdolrazak@student.curtin.edu.au.
authors.forename: Norbaini
authors.initials: N
authors.lastname: Abdol Razak
authors.affiliation: Curtin Health and Innovation Research Institute, Faculty of Health Sciences, Curtin University, 6102 Perth, Australia. omar.elaskalani@postgrad.curtin.edu.au.
authors.forename: Omar
authors.initials: O
authors.lastname: Elaskalani
authors.affiliation: Curtin Health and Innovation Research Institute, Faculty of Health Sciences, Curtin University, 6102 Perth, Australia. pat.metharom@curtin.edu.au.
authors.forename: Pat
authors.initials: P
authors.lastname: Metharom
mesh_terms: D001792:Blood Platelets / Q000378:metabolism; D045744:Cell Line, Tumor; D065206:Extracellular Traps / Q000378:metabolism*; D006801:Humans; D009504:Neutrophils / Q000378:metabolism*; D018384:Oxidative Stress; D010190:Pancreatic Neoplasms / Q000150:complications* / Q000378:metabolism*; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D017382:Reactive Oxygen Species; D013927:Thrombosis / Q000209:etiology*
chemical_list: D017382:Reactive Oxygen Species
keywords: neutrophil extracellular traps; pancreatic cancer; platelets; venous thromboembolism