NETosis in cancer: a critical analysis of the impact of cancer on neutrophil extracellular trap (NET) release in lung cancer patients vs. mice

Arpinati, Ludovica; Shaul, Merav E.; Kaisar-Iluz, Naomi; Mali, Shira; Mahroum, Sojod; Fridlender, Zvi G.

doi:10.1007/s00262-019-02474-x

Cited by 44 publications

(42 citation statements)

References 67 publications

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“…Previous studies have demonstrated that the production of NETs in tumor patients is significantly higher compared with that in healthy controls ( 44 , 45 ). Microenvironmental changes in tumor patients are more likely to stimulate the production of NETs, and tumor cells can release inflammatory factors, such as IL-6, IL-8 and G-CSF, to promote the release of NETs from neutrophils ( 46 , 47 ). The present study revealed that the total number of neutrophils and the percentage of neutrophils in patients with GC did not differ significantly compared with the healthy controls; however, the level of NETs differed between the 2 groups.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil extracellular traps promote gastric cancer metastasis by inducing epithelial‑mesenchymal transition

Zhu

Zou

Yang³

et al. 2021

Int J Mol Med

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The risks of tumor recurrence following the successful resection of the primary tumor have been known for decades; however, the precise mechanisms underlying treatment failures remain unknown. The formation of neutrophil extracellular traps (NETs) has increasingly been demonstrated to be associated with thrombi formation in cancer patients, as well as with the development and metastasis of cancer. The present study demonstrated that the level of peripheral blood NETs in patients with gastric cancer (Gc) was associated with tumor progression, and patients with stage III/IV disease exhibited significant differences compared with the healthy controls and patients with stage I/II disease, which may be associated with an increased risk of metastasis. In addition, plasma from patients with stage III/IV Gc was more prone to stimulate neutrophils to form NETs; thus, it was hypothesized that the formation of NETs may be affected by the tumor microenvironment. A higher deposition of NETs in Gc tissues compared with normal resection margins was also identified. In vitro, following treatment with phorbol myristate acetate, which promotes the formation of NETs, or with dNAse-1/GSK-484, which inhibits the formation of NETs, it was found that the tumor migratory ability was altered; however, no significant changes were observed in cell proliferation and cell cycle progression. Epithelial-mesenchymal transition (EMT) is a key event associated with dissemination and metastasis in Gc pathogenesis. Finally, the present study demonstrated that NETs promote a more aggressive mesenchymal phenotype and promote the progression of Gc in vitro and in vivo. On the whole, to the best of our knowledge, the present study reports a previously unknown role of NETs in the regulation of Gc, which is associated with EMT and migration. Therefore, targeting NETs may prove to be therapeutically beneficial.

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Section: Discussionmentioning

confidence: 99%

Neutrophil extracellular traps promote gastric cancer metastasis by inducing epithelial‑mesenchymal transition

Zhu

Zou

Yang³

et al. 2021

Int J Mol Med

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“…Interestingly, in colorectal cancer (CRC) patients, Tohme et al discovered, serum NETs levels of patients undergoing hepatectomy markedly elevated, distinguish from that of healthy controls, and greater risk of poor prognosis [35] . Besides, abundant studies have hinted G-CSF in aggravating NETs formation in preclinical tumor experiments [32,36,37] . Unexpectedly, differ from patients with myelosuppression, rhG-CSF was signi cantly associated with DOM in NSCLC patients without myelosuppression in the result of our analyses.…”

Section: Discussionmentioning

confidence: 99%

Recombinant Human Granulocyte Colony-Stimulating Factor is Associated with Increased Risk of Metastasis in NSCLC Patients Following Postoperative Chemotherapy: A Retrospective Cohort Study

Wang

Chen

Yuan

et al. 2021

Preprint

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Background: Recombinant human granulocyte colony-stimulating factor (rhG-CSF), which can reduce neutropenia events, is widely used in cancer patients receiving chemotherapy. However, the effects of rhG-CSF on distant organ metastasis (DOM) in non-small cell lung cancer (NSCLC) patients following postoperative chemotherapy remain unclear.Methods: A retrospective cohort study was performed on NSCLC patients who suffered complete surgical resection and postoperative system chemotherapy at The First Affiliated Hospital of Nanchang University between 1 January 2012 and 31 December 2017. The effect of rhG-CSF on DOM was assessed, regulating with other confounding factors using Cox regression analyses.Results: We identified 307 NSCLC patients who received postoperative system chemotherapy (n=246 rhG-CSF group, n=61 No rhG-CSF group). The incidence of DOM in postoperative NSCLC patients with rhG-CSF treatment was observably higher than without rhG-CSF (48.3% vs. 27.9%, p<0.05). Univariate regression analysis revealed that rhG-CSF and clinical stage were the independent risk factor of Metastasis-free survival (MFS) (p<0.05). rhG-CSF users had a higher risk of DOM (adjusted HR: 2.33, 95% CI: 1.31-4.15) than nonusers of rhG-CSF. The association between rhG-CSF and risk of DOM was significant only among patients presenting with myelosuppression (HR: 3.34, 95% CI: 1.86-6.02), not among those without myelosuppression (HR: 0.71, 95% CI: 0.17-2.94, Interaction p-value<0.01). The risk increased with higher dosage density of rhG-CSF use, comparing those using rhG-CSF versus no users (p for trend<0.001).Conclusion These analyses indicated that rhG-CSF use is related to DOM following postoperative chemotherapy in NSCLC.

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“…In recent decades, NETs have been determined to play an important part in host defense and pathologic inflammation. Evidence shows that NETs are associated with pathophysiological processes in cardiovascular disease [64,65], pancreatitis [66], asthma [67,68], COPD [69,70], and cancer [71]. As a protein-DNA complex, the main structures of NETs are extracellular DNA, histone, and many types of peptides, such as neutrophil elastase, myeloperoxidase, lactoferrin, gelatinase, and cathelicidins [72].…”

Section: Alpha-linolenic Acid (Omega-3)mentioning

confidence: 99%

Role of specialized pro-resolving lipid mediators in pulmonary inflammation diseases: mechanisms and development

Yang

et al. 2021

Respir Res

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Inflammation is an essential mechanism of various diseases. The development and resolution of inflammation are complex immune-modulation processes which induce the involvement of various types of immune cells. Specialized pro-resolving lipid mediators (SPMs) have been demonstrated to be signaling molecules in inflammation. SPMs are involved in the pathophysiology of different diseases, especially respiratory diseases, including asthma, pneumonia, and chronic obstructive pulmonary disease. All of these diseases are related to the inflammatory response and its persistence. Therefore, a deeper understanding of the mechanisms and development of inflammation in respiratory disease, and the roles of the SPM family in the resolution process, might be useful in the quest for novel therapies and preventive measures for pulmonary diseases.

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NETosis in cancer: a critical analysis of the impact of cancer on neutrophil extracellular trap (NET) release in lung cancer patients vs. mice

Cited by 44 publications

References 67 publications

Neutrophil extracellular traps promote gastric cancer metastasis by inducing epithelial‑mesenchymal transition

Neutrophil extracellular traps promote gastric cancer metastasis by inducing epithelial‑mesenchymal transition

Recombinant Human Granulocyte Colony-Stimulating Factor is Associated with Increased Risk of Metastasis in NSCLC Patients Following Postoperative Chemotherapy: A Retrospective Cohort Study

Role of specialized pro-resolving lipid mediators in pulmonary inflammation diseases: mechanisms and development

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