scholarly journals Tumor-Derived Exosomes Induce the Formation of Neutrophil Extracellular Traps: Implications For The Establishment of Cancer-Associated Thrombosis

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Ana C. Leal ◽  
Daniella M. Mizurini ◽  
Tainá Gomes ◽  
Natalia C. Rochael ◽  
Elvira M. Saraiva ◽  
...  
Keyword(s):  
Neutrophil Extracellular Traps ◽  
Extracellular Traps ◽  
Cancer Associated Thrombosis

scholarly journals The Emerging Role of Neutrophil Extracellular Traps in Arterial, Venous and Cancer-Associated Thrombosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Yilu Zhou ◽  
Weimin Tao ◽  
Fuyi Shen ◽  
Weijia Du ◽  
Zhendong Xu ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Neutrophil Extracellular Traps ◽  
Vital Role ◽  
Extracellular Traps ◽  
Protein Components ◽  
Cancer Associated Thrombosis ◽  
Coagulation Pathway

Neutrophils play a vital role in the formation of arterial, venous and cancer-related thrombosis. Recent studies have shown that in a process known as NETosis, neutrophils release proteins and enzymes complexed to DNA fibers, collectively called neutrophil extracellular traps (NETs). Although NETs were originally described as a way for the host to capture and kill bacteria, current knowledge indicates that NETs also play an important role in thrombosis. According to recent studies, the destruction of vascular microenvironmental homeostasis and excessive NET formation lead to pathological thrombosis. In vitro experiments have found that NETs provide skeletal support for platelets, red blood cells and procoagulant molecules to promote thrombosis. The protein components contained in NETs activate the endogenous coagulation pathway to promote thrombosis. Therefore, NETs play an important role in the formation of arterial thrombosis, venous thrombosis and cancer-related thrombosis. This review will systematically summarize and explain the study of NETs in thrombosis in animal models and in vivo experiments to provide new targets for thrombosis prevention and treatment.

Sciellin stimulates gallbladder cancer proliferation and tumor-association thrombosis via formation of neutrophil extracellular traps

2020 ◽  
Author(s):  
Yang Li ◽  
Tai Ren ◽  
Bo Yang ◽  
Huijie Miao ◽  
Liguo Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Gallbladder Cancer ◽  
Cell Biology ◽  
Tumor Development ◽  
Neutrophil Extracellular Traps ◽  
Cancer Proliferation ◽  
Extracellular Traps ◽  
Egfr Expression ◽  
Tumor Association ◽  
Cancer Associated Thrombosis

Abstract Background：Apart from primary tumor development and metastasis, cancer-associated thrombosis is the second cause of cancer death in solid tumor malignancy. However, the mechanistic insight into the development of gallblader cancer (GBC) and cancer-associated thrombosis remains unclear. This study aimed to investigate the mechanistic role of Sciellin （SCEL） in GBC cell proliferation and the development of venous thromboembolism. Methods: The expression level of SCEL was determined by immunohistochemical staining. Roles of SCEL in gallbladder cancer cell were determined by molecular and cell biology methodsResults: SCEL was markedly upregulated in GBC and associated with advanced TNM stages and a poor prognosis. Furthermore, SCEL interacted with EGFR and stabilized EGFR expression that activates downstream PI3K and Akt pathway, leading to cell proliferation. In addition, SCEL induces tumor cell IL-8 production that stimulates the formation of neutrophil extracellular traps (NETs), accelerating thromboembolism. In xenografts, SCEL-expressing GBCs developed larger tumors and thrombosis compared with control cells. Conclusions: The present results indicate that SCEL promotes GBC cell proliferation and induces NET-associated thrombosis , thus serving as a potential therapeutic target.

scholarly journals Role of Sciellin in gallbladder cancer proliferation and formation of neutrophil extracellular traps

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yang Li ◽  
Ruiyan Yuan ◽  
Tai Ren ◽  
Bo Yang ◽  
Huijie Miao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Gallbladder Cancer ◽  
Cell Biology ◽  
Tumor Development ◽  
Neutrophil Extracellular Traps ◽  
Cancer Proliferation ◽  
Extracellular Traps ◽  
Egfr Expression ◽  
Cancer Associated Thrombosis

AbstractApart from primary tumor development and metastasis, cancer-associated thrombosis is the second cause of cancer death in solid tumor malignancy. However, the mechanistic insight into the development of gallbladder cancer (GBC) and cancer-associated thrombosis remains unclear. This study aimed to investigate the mechanistic role of Sciellin (SCEL) in GBC cell proliferation and the development of venous thromboembolism. The expression level of SCEL was determined by immunohistochemical staining. Roles of SCEL in gallbladder cancer cell were determined by molecular and cell biology methods. SCEL was markedly upregulated in GBC and associated with advanced TNM stages and a poor prognosis. Furthermore, SCEL interacted with EGFR and stabilized EGFR expression that activates downstream PI3K and Akt pathway, leading to cell proliferation. In addition, SCEL induces tumor cell IL-8 production that stimulates the formation of neutrophil extracellular traps (NETs), accelerating thromboembolism. In xenografts, SCEL-expressing GBCs developed larger tumors and thrombosis compared with control cells. The present results indicate that SCEL promotes GBC cell proliferation and induces NET-associated thrombosis, thus serving as a potential therapeutic target.

scholarly journals The regulatory mechanism of neutrophil extracellular traps in cancer biological behavior

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hui Wang ◽  
Yiyin Zhang ◽  
Qianling Wang ◽  
Xiaoli Wei ◽  
Hua Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Host Defense ◽  
Regulatory Mechanism ◽  
Neutrophil Extracellular Traps ◽  
Biological Behavior ◽  
Molecular Pathways ◽  
The Past ◽  
Extracellular Traps ◽  
Promote Tumor Growth ◽  
Cancer Associated Thrombosis

AbstractAs the predominant host defense against pathogens, neutrophil extracellular traps (NETs) have attracted increasing attention due to their vital roles in infectious inflammation in the past few years. Interestingly, NETs also play important roles in noninfectious conditions, such as rheumatism and cancer. The process of NETs formation can be regulated and the form of cell death accompanied by the formation of NETs is regarded as “NETosis”. A large amount of evidence has confirmed that many stimuli can facilitate the release of NETs from neutrophils. Furthermore, it has been illustrated that NETs promote tumor growth and progression via many molecular pathways. Meanwhile, NETs also can promote metastasis in many kinds of cancers based on multiple studies. In addition, some researchs have found that NETs can promote coagulation and cancer-associated thrombosis. In the present review, it will highlight how NETosis, which is stimulated by various stimuli and signaling pathways, affects cancer biological behaviors via NETs. Given their crucial roles in cancer, NETs will become possible therapeutic targets for inhibiting proliferation, metastasis and thrombosis in cancer patients.

scholarly journals Gastric Cancer-Induced Neutrophil Extracellular Traps: A Potent Mediator of Cancer Associated Thrombosis

2021 ◽  
Author(s):  
Jiacheng Li ◽  
Xiaoming Zou ◽  
Shifeng Yang ◽  
Jiaqi Jin ◽  
Lei Zhu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Flow Cytometry ◽  
Activated Protein C ◽  
Neutrophil Extracellular Traps ◽  
Mice Model ◽  
Tissue Samples ◽  
Extracellular Traps ◽  
Cancer Associated Thrombosis

Abstract Background: Development of venous thromboembolism (VTE) is associated with high mortalities among gastric cancer (GC) patients. Neutrophil extracellular traps (NETs) have been reported to correlated to procoagulant and prothrombotic in some diseases. We aimed to clarify that NETs participates in the development of cancer-associated thrombosis in GC.Method: The level of NETs in blood and tissue samples of patients were analyzed by ELISA and flow cytometry. NETs generation in vitro were observed by immunofluorescence (IF). The NETs procoagulant activity (PCA) was performed by fibrin formation and thrombin-antithrombin complex (TAT) assays. Hypercoagulation of platelets and endothelial cells (ECs) stimulated by NETs were measured by IF and flow cytometry. Thrombosis in vivo was measured in an established mice model of VTE induced by flow stenosis in the inferior vena cave (IVC).Result: NETs are likely to form in blood and tissue samples of GC patients compared with healthy individuals. In vitro studies that GC cells and their conditioned medium (CM), but not gastric mucosal epithelial cell can stimulate NETs releasing from neutrophils. In addition, NETs induced hypercoagulation of platelets by up-regulating the expression of phosphatidylserine (PS) and P-selectin on the cells. Furhter, NETs stimulate adhesion of normal platelets on glass surfaces. Similarly, NETs trigger the conversion of ECs to hypercoagulable phenotypes by down-regulating the expression of their intercellular tight junctions but up-regulating that of tissue factor (TF). Treatment of normal platelets or ECs with NETs augmented the level of plasma fibrin generation and TAT complex. Meanwhile, in the models of IVC stenosis, tumor-bearing mice demonstrate stronger ability to form thrombi and NETs were abundantly accumulated in the thrombi compared with control mice. Notably, combination of DNase-1, activated protein C (APC) and Sivelestat markedly abolished the PCA of NETs.Conclusion: Our findings demonstrate that GC-induced NETs strongly increase the risks of VTE development both in vitro and in vivo. Given that inhibitors of NETs disrupt hypercoagulation, NETs are potential therapeutic target against VTE.

Neutrophil Extracellular Traps Participate in the Development of Gastric Cancer Associated Thrombosis

2021 ◽  
Author(s):  
Jiacheng Li ◽  
Xiaoming Zou ◽  
Shifeng Yang ◽  
Jiaqi Jin ◽  
Lei Zhu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Activated Protein C ◽  
Neutrophil Extracellular Traps ◽  
Tissue Samples ◽  
Extracellular Traps ◽  
Fibrin Formation ◽  
Inferior Vena Cave ◽  
Cancer Associated Thrombosis

Abstract Background: Development of venous thromboembolism (VTE) is associated with high mortalities among gastric cancer (GC) patients. Neutrophil extracellular traps (NETs) have been reported to correlated with prothrombotic state in some diseases. We hypothesize that NETs participate in the development of GC-associated thrombosis.Methods: The level of NETs in blood and tissue samples of patients were analyzed by ELISA, flow cytometry and immunofluorescence (IF). NETs generation and hypercoagulation of platelets and endothelial cells (ECs) in vitro were observed by IF. NETs procoagulant activity (PCA) was performed by fibrin formation and thrombin-antithrombin complex (TAT) assays. Thrombosis in vivo was measured in murine model induced by flow stenosis in the inferior vena cave (IVC).Results: NETs were likely to form in blood and tissue samples of GC patients compared with healthy individuals. In vitro studies that GC cells and their conditioned medium (CM), but not gastric mucosal epithelial cell can stimulate NETs releasing from neutrophils. In addition, NETs induced hypercoagulable state of platelets by up-regulating the expression of phosphatidylserine (PS) and P-selectin on the cells. Furhter, NETs stimulated adhesion of normal platelets on glass surfaces. Similarly, NETs triggered the conversion of ECs to hypercoagulable phenotypes by down-regulating the expression of their intercellular tight junctions but up-regulating that of tissue factor (TF). Treatment of normal platelets or ECs with NETs augmented the level of plasma fibrin formation and TAT complex. Meanwhile, in the models of IVC stenosis, tumor-bearing mice showed stronger ability to form thrombi and NETs were abundantly accumulated in the thrombi compared with control mice. Notably, combination of DNase-1, activated protein C (APC) and Sivelestat markedly abolished the PCA of NETs.Conclusions: Our findings demonstrate that GC-induced NETs strongly increase the risks of VTE development both in vitro and in vivo. NETs are potential therapeutic targets in the prevention and treatment of VTE in GC patients.

scholarly journals Novel Aspects of Extracellular Vesicles as Mediators of Cancer-Associated Thrombosis

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 716 ◽  
Author(s):  
Vitor H. Almeida ◽  
Araci M. R. Rondon ◽  
Tainá Gomes ◽  
Robson Q. Monteiro
Keyword(s):  
Platelet Aggregation ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Neutrophil Extracellular Traps ◽  
Cancer Type ◽  
Initiator Protein ◽  
Extracellular Traps ◽  
Cancer Types ◽  
Cancer Associated Thrombosis

The establishment of prothrombotic states during cancer progression is well reported but the precise mechanisms underlying this process remain elusive. A number of studies have implicated the presence of the clotting initiator protein, tissue factor (TF), in circulating tumor-derived extracellular vesicles (EVs) with thrombotic manifestations in certain cancer types. Tumor cells, as well as tumor-derived EVs, may activate and promote platelet aggregation by TF-dependent and independent pathways. Cancer cells and their secreted EVs may also facilitate the formation of neutrophil extracellular traps (NETs), which may contribute to thrombus development. Alternatively, the presence of polyphosphate (polyP) in tumor-derived EVs may promote thrombosis through a TF-independent route. We conclude that the contribution of EVs to cancer coagulopathy is quite complex, in which one or more mechanisms may take place in a certain cancer type. In this context, strategies that could attenuate the crosstalk between the proposed pro-hemostatic routes could potentially reduce cancer-associated thrombosis.

scholarly journals Modulation of Cellular NAD+ Attenuates Cancer-Associated Hypercoagulability and Thrombosis via the Inhibition of Tissue Factor and Formation of Neutrophil Extracellular Traps

2021 ◽  
Vol 22 (21) ◽  
pp. 12085
Author(s):  
Wa Cao ◽  
Meng-Yu Zhu ◽  
Seung-Hoon Lee ◽  
Su-Bin Lee ◽  
Hyung-Jin Kim ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Inflammatory Responses ◽  
Vascular Endothelial Cells ◽  
Treatment Strategies ◽  
Neutrophil Extracellular Traps ◽  
Sirtuin 1 ◽  
Quinone Oxidoreductase ◽  
Extracellular Traps ◽  
Tumor Bearing ◽  
Cancer Associated Thrombosis

Cancer-associated thrombosis is the second-leading cause of mortality in patients with cancer and presents a poor prognosis, with a lack of effective treatment strategies. NAD(P)H quinone oxidoreductase 1 (NQO1) increases the cellular nicotinamide adenine dinucleotide (NAD+) levels by accelerating the oxidation of NADH to NAD+, thus playing important roles in cellular homeostasis, energy metabolism, and inflammatory responses. Using a murine orthotopic 4T1 breast cancer model, in which multiple thrombi are generated in the lungs at the late stage of cancer development, we investigated the effects of regulating the cellular NAD+ levels on cancer-associated thrombosis. In this study, we show that dunnione (a strong substrate of NQO1) attenuates the prothrombotic state and lung thrombosis in tumor-bearing mice by inhibiting the expression of tissue factor and formation of neutrophil extracellular traps (NETs). Dunnione increases the cellular NAD+ levels in lung tissues of tumor-bearing mice to restore the declining sirtuin 1 (SIRT1) activity, thus deacetylating nuclear factor-kappa B (NF-κB) and preventing the overexpression of tissue factor in bronchial epithelial and vascular endothelial cells. In addition, we demonstrated that dunnione abolishes the ability of neutrophils to generate NETs by suppressing histone acetylation and NADPH oxidase (NOX) activity. Overall, our results reveal that the regulation of cellular NAD+ levels by pharmacological agents may inhibit pulmonary embolism in tumor-bearing mice, which may potentially be used as a viable therapeutic approach for the treatment of cancer-associated thrombosis.

Sign in / Sign up

Export Citation Format

Share Document