The role of neutrophil extracellular traps in cancer progression, metastasis and therapy

Chen, Yue; Hu, Haoyue; Tan, Songtao; Dong, Qionglan; Wang, Yi; Zhang, Huan; He, Jiang

doi:10.1186/s40164-022-00345-3

Cited by 35 publications

(27 citation statements)

References 127 publications

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“…High amounts of tumor-infiltrating neutrophils are associated with the adverse outcomes of BC patients. The pro-tumor phenotype of neutrophils is in part influenced by their ability to produce NETs [ 24 ]. Therefore, we performed bioinformatics analysis of the relationship among NETs, neutrophils, and BC.…”

Section: Resultsmentioning

confidence: 99%

Dihydrotanshinone I Inhibits the Lung Metastasis of Breast Cancer by Suppressing Neutrophil Extracellular Traps Formation

Zhao

Liang

Sun

et al. 2022

IJMS

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Breast cancer (BC) is a common female malignancy, worldwide. BC death is predominantly caused by lung metastasis. According to previous studies, Dihydrotanshinone I (DHT), a bioactive compound in Salvia miltiorrhiza Bunge (S. miltiorrhiza), has inhibitory effects on numerous cancers. Here, we investigated the anti-metastatic effect of DHT on BC, where DHT more strongly inhibited the growth of BC cells (MDA-MB-231, 4T1, MCF-7, and SKBR-3) than breast epithelial cells (MCF-10a). Additionally, DHT repressed the wound healing, invasion, and migration activities of 4T1 cells. In the 4T1 spontaneous metastasis model, DHT (20 mg/kg) blocked metastasis progression and distribution in the lung tissue by 74.9%. DHT reversed the formation of neutrophil extracellular traps (NETs) induced by phorbol 12-myristate 13-acetate, as well as ameliorated NETs-induced metastasis. Furthermore, it inhibited Ly6G+Mpo+ neutrophils infiltration and H3Cit expression in the lung tissues. RNA sequencing, western blot, and bioinformatical analysis indicated that TIMP1 could modulate DHT acting on lung metastasis inhibition. The study demonstrated a novel suppression mechanism of DHT on NETs formation to inhibit BC metastasis.

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Section: Resultsmentioning

confidence: 99%

Dihydrotanshinone I Inhibits the Lung Metastasis of Breast Cancer by Suppressing Neutrophil Extracellular Traps Formation

Zhao

Liang

Sun

et al. 2022

IJMS

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“…Single-cell RNA sequencing analysis showed that the infiltration of N2 TANs was significantly higher in a hybrid cell-derived tumor microenvironment. N2 TANs can promote the growth and metastasis of tumors by secreting enzymes or cytokines that can reconstruct the extracellular matrix, promote angiogenesis, and facilitate immune escape [ 40 , 65 ]. The secretome analysis based on RNA-seq and cytokine array showed that the expression of chemokines that can recruit neutrophils, monocytes, and macrophages, including Ccl2, Ccl3, Cxcl1, Cxcl3, and Cxcl5, was significantly up-regulated in hybrid cells.…”

Section: Discussionmentioning

confidence: 99%

Myeloid-like tumor hybrid cells in bone marrow promote progression of prostate cancer bone metastasis

Huang

et al. 2023

J Hematol Oncol

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Background Bone metastasis is the leading cause of death in patients with prostate cancer (PCa) and currently has no effective treatment. Disseminated tumor cells in bone marrow often obtain new characteristics to cause therapy resistance and tumor recurrence. Thus, understanding the status of disseminated prostate cancer cells in bone marrow is crucial for developing a new treatment. Methods We analyzed the transcriptome of disseminated tumor cells from a single cell RNA-sequencing data of PCa bone metastases. We built a bone metastasis model through caudal artery injection of tumor cells, and sorted the tumor hybrid cells by flow cytometry. We performed multi-omics analysis, including transcriptomic, proteomic and phosphoproteomic analysis, to compare the difference between the tumor hybrid cells and parental cells. In vivo experiments were performed to analyze the tumor growth rate, metastatic and tumorigenic potential, drug and radiation sensitivity in hybrid cells. Single cell RNA-sequencing and CyTOF were performed to analyze the impact of hybrid cells on tumor microenvironment. Results Here, we identified a unique cluster of cancer cells in PCa bone metastases, which expressed myeloid cell markers and showed a significant change in pathways related to immune regulation and tumor progression. We found that cell fusion between disseminated tumor cells and bone marrow cells can be source of these myeloid-like tumor cells. Multi-omics showed the pathways related to cell adhesion and proliferation, such as focal adhesion, tight junction, DNA replication, and cell cycle, were most significantly changed in these hybrid cells. In vivo experiment showed hybrid cells had a significantly increased proliferative rate, and metastatic potential. Single cell RNA-sequencing and CyTOF showed tumor-associated neutrophils/monocytes/macrophages were highly enriched in hybrid cells-induced tumor microenvironment with a higher immunosuppressive capacity. Otherwise, the hybrid cells showed an enhanced EMT phenotype with higher tumorigenicity, and were resistant to docetaxel and ferroptosis, but sensitive to radiotherapy. Conclusion Taken together, our data demonstrate that spontaneous cell fusion in bone marrow can generate myeloid-like tumor hybrid cells that promote the progression of bone metastasis, and these unique population of disseminated tumor cells can provide a potential therapeutic target for PCa bone metastasis.

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“…Subsequently, neutrophilic destroy capillaries cause blood vessel leakage, which are connected to impaired graft function. TLR4 pathway in vascular endothelial cells in synergy with subsequent NADPH oxidase 4 (NOX4) facilitate neutrophil arrest 68,145 . The formation of neutrophil extracellular traps in the damaged lungs and the destroy prevent vascular leakage as well as ameliorate primary graft dysfunction.…”

Section: The Key Molecular Mechanisms Underlying Necroptosis Of Speci...mentioning

confidence: 99%

“…TLR4 pathway in vascular endothelial cells in synergy with subsequent NADPH oxidase 4 (NOX4) facilitate neutrophil arrest. 68,145 The formation of neutrophil extracellular traps in the damaged lungs and the destroy prevent vascular leakage as well as ameliorate primary graft dysfunction. Thus, neutrophils are a key mediator of primary graft dysfunction following lung transplantation, offering treatment targets for patients who currently receive only supportive care.…”

Section: Neutrophilsmentioning

confidence: 99%

Cell type‐specific molecular mechanisms and implications of necroptosis in inflammatory respiratory diseases

Guo,

Zhou,

Wang

et al. 2023

Immunological Reviews

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SummaryNecroptosis is generally considered as an inflammatory cell death form. The core regulators of necroptotic signaling are receptor‐interacting serine–threonine protein kinases 1 (RIPK1) and RIPK3, and the executioner, mixed lineage kinase domain‐like pseudokinase (MLKL). Evidence demonstrates that necroptosis contributes profoundly to inflammatory respiratory diseases that are common public health problem. Necroptosis occurs in nearly all pulmonary cell types in the settings of inflammatory respiratory diseases. The influence of necroptosis on cells varies depending upon the type of cells, tissues, organs, etc., which is an important factor to consider. Thus, in this review, we briefly summarize the current state of knowledge regarding the biology of necroptosis, and focus on the key molecular mechanisms that define the necroptosis status of specific cell types in inflammatory respiratory diseases. We also discuss the clinical potential of small molecular inhibitors of necroptosis in treating inflammatory respiratory diseases, and describe the pathological processes that engage cross talk between necroptosis and other cell death pathways in the context of respiratory inflammation. The rapid advancement of single‐cell technologies will help understand the key mechanisms underlying cell type‐specific necroptosis that are critical to effectively treat pathogenic lung infections and inflammatory respiratory diseases.

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The role of neutrophil extracellular traps in cancer progression, metastasis and therapy

Cited by 35 publications

References 127 publications

Dihydrotanshinone I Inhibits the Lung Metastasis of Breast Cancer by Suppressing Neutrophil Extracellular Traps Formation

Dihydrotanshinone I Inhibits the Lung Metastasis of Breast Cancer by Suppressing Neutrophil Extracellular Traps Formation

Myeloid-like tumor hybrid cells in bone marrow promote progression of prostate cancer bone metastasis

Cell type‐specific molecular mechanisms and implications of necroptosis in inflammatory respiratory diseases

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