Neutrophil Extracellular Trap Production in Patients with Colorectal Cancer In Vitro

Purpose. Neutrophil Extracellular Traps (NETs) are extracellular neutrophil derived DNA webs which have been implicated in cancer progression and in the development of metastases. NETs production in patients with colorectal cancer was investigated to elucidate their role and prognostic significance....

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Main Authors: J. J. R. Richardson, C. Hendrickse, F. Gao-Smith, D. R. Thickett
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:International Journal of Inflammation
Online Access:http://dx.doi.org/10.1155/2017/4915062
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author J. J. R. Richardson
C. Hendrickse
F. Gao-Smith
D. R. Thickett
author_facet J. J. R. Richardson
C. Hendrickse
F. Gao-Smith
D. R. Thickett
author_sort J. J. R. Richardson
collection DOAJ
description Purpose. Neutrophil Extracellular Traps (NETs) are extracellular neutrophil derived DNA webs which have been implicated in cancer progression and in the development of metastases. NETs production in patients with colorectal cancer was investigated to elucidate their role and prognostic significance. Methods. Systemic neutrophils were isolated from consecutive patients with colorectal cancer and from age-matched healthy volunteers. Neutrophils were stimulated to produce NETs which were quantified by a measure of the fluorescence of the extracellular DNA. The impact of cancer location, tumour stage, and patient outcomes (complications, length of stay, and mortality) on NET production was investigated. Results. Quantification of NET formation was performed in patients with colorectal cancer (n=45) and in well-matched healthy individuals (n=20). Significant increases in NETs production in response to no stimulant (9,735 AFU versus 11347 AFU, p=0.0209), IL-8 (8,644 AFU versus 11,915 AFU, p=0.0032), and LPS (10,576 AFU versus 12,473 AFU, p=0.0428) were identified in patients with colorectal cancer. A significant increase in NETs production in response to fMLP was detected in patients who developed significant postoperative complications (11,760 AFU versus 18,340 AFU, p=0.0242) and who had a prolonged hospital recovery (9,008 AFU versus 12,530 AFU, p=0.0476). An increase in NETs production was also observed in patients who died, but this did not reach statistical significance. Cancer location and tumour stage did not appear to affect preoperative NETs production. Conclusions. Patients with colorectal cancer have significantly increased NETs production in vitro when compared to healthy volunteers, possibly implicating them in cancer development. Adverse patient outcomes were associated with increased preoperative NETs production, which highlights them as potential therapeutic targets.
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spelling doaj-art-e6324774cf4f4a638adccbc2744bdbc62025-02-03T05:54:12ZengWileyInternational Journal of Inflammation2090-80402042-00992017-01-01201710.1155/2017/49150624915062Neutrophil Extracellular Trap Production in Patients with Colorectal Cancer In VitroJ. J. R. Richardson0C. Hendrickse1F. Gao-Smith2D. R. Thickett3Institute of Inflammation and Ageing, College of Medical and Dental Sciences, The University of Birmingham, Birmingham B15 2TT, UKDepartment of Colorectal Surgery, Heart of England NHS Foundation Trust, Birmingham B9 5SS, UKInstitute of Inflammation and Ageing, College of Medical and Dental Sciences, The University of Birmingham, Birmingham B15 2TT, UKInstitute of Inflammation and Ageing, College of Medical and Dental Sciences, The University of Birmingham, Birmingham B15 2TT, UKPurpose. Neutrophil Extracellular Traps (NETs) are extracellular neutrophil derived DNA webs which have been implicated in cancer progression and in the development of metastases. NETs production in patients with colorectal cancer was investigated to elucidate their role and prognostic significance. Methods. Systemic neutrophils were isolated from consecutive patients with colorectal cancer and from age-matched healthy volunteers. Neutrophils were stimulated to produce NETs which were quantified by a measure of the fluorescence of the extracellular DNA. The impact of cancer location, tumour stage, and patient outcomes (complications, length of stay, and mortality) on NET production was investigated. Results. Quantification of NET formation was performed in patients with colorectal cancer (n=45) and in well-matched healthy individuals (n=20). Significant increases in NETs production in response to no stimulant (9,735 AFU versus 11347 AFU, p=0.0209), IL-8 (8,644 AFU versus 11,915 AFU, p=0.0032), and LPS (10,576 AFU versus 12,473 AFU, p=0.0428) were identified in patients with colorectal cancer. A significant increase in NETs production in response to fMLP was detected in patients who developed significant postoperative complications (11,760 AFU versus 18,340 AFU, p=0.0242) and who had a prolonged hospital recovery (9,008 AFU versus 12,530 AFU, p=0.0476). An increase in NETs production was also observed in patients who died, but this did not reach statistical significance. Cancer location and tumour stage did not appear to affect preoperative NETs production. Conclusions. Patients with colorectal cancer have significantly increased NETs production in vitro when compared to healthy volunteers, possibly implicating them in cancer development. Adverse patient outcomes were associated with increased preoperative NETs production, which highlights them as potential therapeutic targets.http://dx.doi.org/10.1155/2017/4915062
spellingShingle J. J. R. Richardson
C. Hendrickse
F. Gao-Smith
D. R. Thickett
Neutrophil Extracellular Trap Production in Patients with Colorectal Cancer In Vitro
International Journal of Inflammation
title Neutrophil Extracellular Trap Production in Patients with Colorectal Cancer In Vitro
title_full Neutrophil Extracellular Trap Production in Patients with Colorectal Cancer In Vitro
title_fullStr Neutrophil Extracellular Trap Production in Patients with Colorectal Cancer In Vitro
title_full_unstemmed Neutrophil Extracellular Trap Production in Patients with Colorectal Cancer In Vitro
title_short Neutrophil Extracellular Trap Production in Patients with Colorectal Cancer In Vitro
title_sort neutrophil extracellular trap production in patients with colorectal cancer in vitro
url http://dx.doi.org/10.1155/2017/4915062
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AT fgaosmith neutrophilextracellulartrapproductioninpatientswithcolorectalcancerinvitro
AT drthickett neutrophilextracellulartrapproductioninpatientswithcolorectalcancerinvitro