Pancreatic cancer-induced neutrophil extracellular traps: A potential contributor to cancer-associated thrombosis

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...

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Main Authors: Razak, N., Elaskalani, O., Metharom, Pat
Format: Journal Article
Published: MDPI AG 2017
Online Access:http://hdl.handle.net/20.500.11937/51506
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author Razak, N.
Elaskalani, O.
Metharom, Pat
author_facet Razak, N.
Elaskalani, O.
Metharom, Pat
author_sort Razak, N.
building Curtin Institutional Repository
collection Online Access
description 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.
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spelling curtin-20.500.11937-515062021-01-08T07:54:28Z Pancreatic cancer-induced neutrophil extracellular traps: A potential contributor to cancer-associated thrombosis Razak, N. Elaskalani, O. Metharom, Pat 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. 2017 Journal Article http://hdl.handle.net/20.500.11937/51506 10.3390/ijms18030487 http://creativecommons.org/licenses/by/4.0/ MDPI AG fulltext
spellingShingle Razak, N.
Elaskalani, O.
Metharom, Pat
Pancreatic cancer-induced neutrophil extracellular traps: A potential contributor to cancer-associated thrombosis
title Pancreatic cancer-induced neutrophil extracellular traps: A potential contributor to cancer-associated thrombosis
title_full Pancreatic cancer-induced neutrophil extracellular traps: A potential contributor to cancer-associated thrombosis
title_fullStr Pancreatic cancer-induced neutrophil extracellular traps: A potential contributor to cancer-associated thrombosis
title_full_unstemmed Pancreatic cancer-induced neutrophil extracellular traps: A potential contributor to cancer-associated thrombosis
title_short Pancreatic cancer-induced neutrophil extracellular traps: A potential contributor to cancer-associated thrombosis
title_sort pancreatic cancer-induced neutrophil extracellular traps: a potential contributor to cancer-associated thrombosis
url http://hdl.handle.net/20.500.11937/51506