Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis
Jonathan Cools-Lartigue,Jonathan Spicer,Braedon McDonald,Stephen Gowing,Simon C. Chow,Betty Giannias,Paul Kubes,Lorenzo E. Ferri +7 more
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TLDR
It is reported that circulating tumor cells become trapped within NETs in vitro under static and dynamic conditions and NETs are identified as potential therapeutic targets in the context of systemic infection.Abstract:
The majority of patients with cancer undergo at least one surgical procedure as part of their treatment. Severe postsurgical infection is associated with adverse oncologic outcomes; however, the mechanisms underlying this phenomenon are unclear. Emerging evidence suggests that neutrophils, which function as the first line of defense during infections, facilitate cancer progression. Neutrophil extracellular traps (NETs) are extracellular neutrophil-derived DNA webs released in response to inflammatory cues that trap and kill invading pathogens. The role of NETs in cancer progression is entirely unknown. We report that circulating tumor cells become trapped within NETs in vitro under static and dynamic conditions. In a murine model of infection using cecal ligation and puncture, we demonstrated microvascular NET deposition and consequent trapping of circulating lung carcinoma cells within DNA webs. NET trapping was associated with increased formation of hepatic micrometastases at 48 hours and gross metastatic disease burden at 2 weeks following tumor cell injection. These effects were abrogated by NET inhibition with DNAse or a neutrophil elastase inhibitor. These findings implicate NETs in the process of cancer metastasis in the context of systemic infection and identify NETs as potential therapeutic targets.read more
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Lipid-polymer nanoparticles encapsulating curcumin for modulating the vascular deposition of breast cancer cells.
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Candida albicans-Induced NETosis Is Independent of Peptidylarginine Deiminase 4.
Eva Guiducci,Christina Lemberg,Noëmi Küng,Elisabeth M. Schraner,Alexandre Theocharides,Salomé LeibundGut-Landmann +5 more
TL;DR: It is demonstrated that PAD4 is dispensable for C. albicans-induced NETosis, and the limitations of using histone citrullination as a marker for NETs and P AD4−/− mice as a model of NET-deficiency are highlighted.
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Phagocytes as Corrupted Policemen in Cancer-Related Inflammation.
TL;DR: Targeting phagocytes (TAMs and TANs) as corrupted policemen in cancer may pave the way to innovative therapeutic strategies complementing cytoreductive therapies and immunotherapy.
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Differential Signalling and Kinetics of Neutrophil Extracellular Trap Release Revealed by Quantitative Live Imaging
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TL;DR: It is concluded that NET release in primary human neutrophils is dependent on the SYK-PI3K-mTORC2 pathway and that PMA stimulation should be regarded as mechanistically distinct from NET formation induced by natural triggers.
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Fibrin and Fibrinolysis in Cancer.
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