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Role of neutrophils and neutrophil extracellular traps in mice bearing human pancreatic tumors

Citation

Hisada, Y and Grover, S and Maqsood, A and Houston, R and Ay, C and Nouboussie, D and Cooley, B and Wallen, H and Key, N and Thalin, C and Farkas, A and Tenekedjiev, K and Kolev, K and Mackman, N, Role of neutrophils and neutrophil extracellular traps in mice bearing human pancreatic tumors, Research and Practice in Thrombosis and Haemostasis, 3, (51) Article OC30.4. ISSN 2475-0379 (2019) [Contribution to Refereed Journal]


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Abstract

Background : Pancreatic cancer is associated with high incidence of venous thromboembolism (VTE). Neutrophils have been shown to contribute to thrombosis in part by releasing neutrophil extracellular traps (NETs). A recent clinical study showed that increased plasma levels of the NET biomarker, citrullinated histone H3 (H3Cit), are associated with VTE in pancreatic and lung cancer but not in other types of cancer, including breast cancer.

Aims : To determine the contribution of neutrophils and NETs to venous thrombosis in mice bearing human pancreatic tumors.

Methods : Nude mice bearing human pancreatic BxPc- 3 tumors were used. Thrombosis was induced by inferior vena cava stasis.

Results : 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 extracellular DNA. Thrombi from tumor- bearing mice also had thinner fibrin fibers consistent with increased thrombin generation. Importantly, neutrophil depletion and administration of DNase I reduced thrombus size in tumor- bearing but not in control mice.

Conclusions : Our data indicate that neutrophils and NETs contribute to venous thrombosis in a mouse model of pancreatic cancer. Targeting this pathway may prevent VTE in pancreatic cancer patients without increasing bleeding.

Item Details

Item Type:Contribution to Refereed Journal
Keywords:neutrophils, NET, venous thrombosis, mice, pancreatic tumors
Research Division:Information and Computing Sciences
Research Group:Artificial Intelligence and Image Processing
Research Field:Simulation and Modelling
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Medical and Health Sciences
UTAS Author:Tenekedjiev, K (Professor Kiril Tenekedjiev)
ID Code:133928
Year Published:2019
Deposited By:NC Maritime Engineering and Hydrodynamics
Deposited On:2019-07-16
Last Modified:2019-07-16
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