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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Targeting of CCL2-CCR2-Glycosaminoglycan Axis Using a CCL2 Decoy Protein Attenuates Metastasis through Inhibition of Tumor Cell Seeding
Marko Roblek,Elisabeth Strutzmann,Christina Zankl,Tiziana Adage,Mathias Heikenwalder,Mathias Heikenwalder,Aid Atlic,Roland Weis,Andreas J. Kungl,Lubor Borsig +9 more
TL;DR: It is demonstrated that the CCL2-based decoy protein effectively binds to the activated endothelium in lungs and blocks tumor cell extravasation through inhibition of vascular permeability.
Journal ArticleDOI
Inflammation and skeletal metastasis
Hernan Roca,Laurie K. McCauley +1 more
TL;DR: This review focuses on the inflammatory cells, molecules and mechanisms that facilitate the expansion of cancer cells from the primary tumor to their new 'home' in the skeleton.
Journal ArticleDOI
Neutrophil extracellular traps promote peritoneal metastasis of colon cancer cells
Amr A. Al-Haidari,Nader Algethami,Mattias Lepsenyi,Milladur Rahman,Ingvar Syk,Henrik Thorlacius +5 more
TL;DR: The novel findings suggest that targeting NETs might be an effective strategy to antagonize intrabdominal recurrences of colon cancer after cytoreductive surgery in patients with peritoneal carcinomatosis.
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NETosis provides the link between activation of neutrophils on hemodialysis membrane and comorbidities in dialyzed patients.
Marie Korabecna,Vladimir Tesar +1 more
TL;DR: The study of plasma cell-free DNA levels together with markers of NETosis could contribute to the evaluation of the influence of hemodialytic procedure on the immune system of patients.
Journal ArticleDOI
ELISA detection of MPO-DNA complexes in human plasma is error-prone and yields limited information on neutrophil extracellular traps formed in vivo.
Hubert Hayden,Nahla Ibrahim,Johannes Klopf,Branislav Zagrapan,Lisa-Marie Mauracher,Lena Hell,Thomas M. Hofbauer,Anna S. Ondracek,Christian Schoergenhofer,Bernd Jilma,Irene M. Lang,Ingrid Pabinger,Wolf Eilenberg,Christoph Neumayer,Christine Brostjan +14 more
TL;DR: In this paper, the authors used a modified MPO-DNA ELISA protocol to analyze MPO DNA complexes in human blood samples of acute and chronic inflammatory conditions, and found that the use of Fab fragments or immunoglobulins from different species or reversal of the antibody pair led to either a high background or a low dynamic range of detection that did not improve the specificity for plasma samples.
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