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Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis

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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.

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Journal ArticleDOI

Emerging Biological Principles of Metastasis

TL;DR: The cellular and molecular mechanisms involved in metastasis are summarized, with a focus on carcinomas where the most is known, and the general principles of metastasis that have begun to emerge are highlighted.
Journal ArticleDOI

Neutrophil extracellular traps in immunity and disease

TL;DR: The identification of molecules that modulate the release of NETs has helped to refine the view of the role of neutrophils in immune protection, inflammatory and autoimmune diseases and cancer.
Journal ArticleDOI

Neutrophils in cancer: neutral no more

TL;DR: This Review discusses the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets.
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The Cancer Stem Cell Niche: How Essential Is the Niche in Regulating Stemness of Tumor Cells?

TL;DR: This work focuses on the CSC niche and discusses its contribution to tumor initiation and progression and examines the prospects of targeting the niche components as preferable therapeutic targets.
Journal ArticleDOI

Roles of the immune system in cancer: from tumor initiation to metastatic progression.

TL;DR: An update of recent accomplishments, unifying concepts, and future challenges to study tumor-associated immune cells, with an emphasis on metastatic carcinomas are provided.
References
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Journal ArticleDOI

Hydroxylated fullerenes inhibit neutrophil function in fathead minnow (Pimephales promelas Rafinesque, 1820).

TL;DR: Observed changes in gene transcription and neutrophil function indicate potential for hydroxylated fullerenes to interfere with the evolutionary conserved innate immune system responses and encourages the use of fish models in studies of nanoparticle immunotoxicity.
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Two-dimensional kinetics of β2-integrin and ICAM-1 bindings between neutrophils and melanoma cells in a shear flow

TL;DR: Interactions of PMNs with WM9 melanoma cells were investigated to quantify the kinetics of beta 2-integrin and ICAM-1 bindings using a cone-plate viscometer that generates a linear shear flow combined with a two-color flow cytometry technique, providing new quantitative understanding of the biophysical basis of leukocyte-tumor cell interactions mediated by specific receptor-ligand interactions under shearflow conditions.
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Palliative Venting Gastrostomy in Patients with Malignant Bowel Obstruction and Ascites

TL;DR: PDGT is feasible in the majority of patients with MBO and ascites, although there is an inherent risk of major complications, and an intraperitoneal catheter can be used to manage ascites to facilitate PDGT.
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