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Neutrophils and neutrophil extracellular traps enhance venous thrombosis in mice bearing human pancreatic tumors

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Hisada, Y, Grover, SP, Maqsood, A, Houston, R, Ay, C, Noubouossie, DF, Cooley, BC, Wallen, H, Key, NS, Thalin, C, Farkas, AZ, Farkas, VJ, Tenekedjiev, K ORCID: 0000-0003-3549-0671, Kolev, K and Mackman, N 2019 , 'Neutrophils and neutrophil extracellular traps enhance venous thrombosis in mice bearing human pancreatic tumors' , Haematologica, vol. 105, no. 1 , pp. 218-225 , doi: 10.3324/haematol.2019.217083.

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Abstract

Pancreatic cancer is associated with high incidence of venous thromboembolism. Neutrophils have been shown to contribute to thrombosis in part by releasing neutrophil extracellular traps (NETs). A recent study showed that increased plasma levels of the NET biomarker, citrullinated histone H3 (H3Cit), are associated with venous thromboembolism in pancreatic and lung cancer but not in other types of cancer, including breast cancer. In this study, we examined the contribution of neutrophils and NETs to venous thrombosis in nude mice bearing human pancreatic tumors. We found that tumor-bearing mice had increased circulating neutrophil counts and levels of granulocyte-colony stimulating factor, neutrophil elastase, H3Cit and cell-free DNA compared with controls. In addition, thrombi from tumor-bearing mice contained increased levels of the neutrophil marker Ly6G, as well as higher levels of H3Cit and cell-free DNA. Thrombi from tumor-bearing mice also had denser fibrin with thinner fibers consistent with increased thrombin generation. Importantly, either neutrophil depletion or administration of DNase I reduced the thrombus size in tumor-bearing but not in control mice. Our results, together with clinical data, suggest that neutrophils and NETs contribute to venous thrombosis in pancreatic cancer patients.

Item Type: Article
Authors/Creators:Hisada, Y and Grover, SP and Maqsood, A and Houston, R and Ay, C and Noubouossie, DF and Cooley, BC and Wallen, H and Key, NS and Thalin, C and Farkas, AZ and Farkas, VJ and Tenekedjiev, K and Kolev, K and Mackman, N
Keywords: extracellular traps, thrombosis, pancreatic tumors
Journal or Publication Title: Haematologica
Publisher: Ferrata Storti Foundation
ISSN: 0390-6078
DOI / ID Number: 10.3324/haematol.2019.217083
Copyright Information:

Copyright 2020 Ferrata Storti Foundation. Licensed under Creative Commons Attribution-NonCommercial 4.0 International https://creativecommons.org/licenses/by-nc/4.0/legalcode

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