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Journal of Cancer Research and Clinical Oncology

Erschienen in:

24.04.2019 | Original Article – Cancer Research

Neutrophil extracellular traps enhance procoagulant activity in patients with oral squamous cell carcinoma

verfasst von: Baorong Li, Yingmiao Liu, Tenglong Hu, Yan Zhang, Cong Zhang, Tao Li, Chunxu Wang, Zengxiang Dong, Valerie A. Novakovic, Tianshui Hu, Jialan Shi

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 7/2019

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Abstract

Background

Hypercoagulability is a major cancer-associated complication linked to poor patient prognosis. The production of neutrophil extracellular traps (NETs) is increasingly found to be linked with the development and metastasis of cancer, as well as with thrombi formation in cancer patients. We hypothesized that the neutrophil NET release may be triggered by specific cytokines in oral squamous cell carcinoma (OSCC) patients, thereby predisposing them to a hypercoagulable state. Moreover, we have evaluated the interaction between NETs and endothelial cells (ECs).

Methods

NET procoagulant activity was assessed based on fibrin and purified coagulation complex production assays, as well as by measuring coagulation time (CT). We further used confocal microscopy to quantify the exposure of phosphatidylserine (PS), fibrin strands, and cell FVa/Xa binding.

Results

OSCC patients with stage III/IV exhibited elevated plasma NET levels compared to stage I/II or CTR (all P < 0.05). Neutrophils from OSCC patients are predisposed to amplified NET release compared to those from CTR. Furthermore, depleting IL-8, IL-6, and TNF-α led to a reduction in NET release in the plasma. OSCC NETs increased thrombin and fibrin generation and decreased CT significantly (P < 0.05). When NETs were isolated and used to treat ECs, these cells exhibited disrupted morphology by retracting from their cell–cell junctions and convert to a procoagulant phenotype. These effects could be attenuated by approximately 70% using DNase I.

Conclusions

Our findings are consistent with a model wherein OSCC drives a systemic inflammatory state, which, in turn, drives neutrophils to prime and release NETs, which drive the development of a hypercoagulable state. Intervening in this process may be a viable means of disrupting these undesirable coagulation dynamics in stage III/IV OSCC patients.

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Titel: Neutrophil extracellular traps enhance procoagulant activity in patients with oral squamous cell carcinoma
verfasst von: Baorong Li
Yingmiao Liu
Tenglong Hu
Yan Zhang
Cong Zhang
Tao Li
Chunxu Wang
Zengxiang Dong
Valerie A. Novakovic
Tianshui Hu
Jialan Shi
Publikationsdatum: 24.04.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 7/2019
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-019-02922-2

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Neutrophil extracellular traps enhance procoagulant activity in patients with oral squamous cell carcinoma