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
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
Evidence and impact of neutrophil extracellular traps in malignant melanoma.
Fiona Schedel,Sarah Mayer-Hain,Karin Ingrid Pappelbaum,Dieter Metze,Martin Stock,Tobias Goerge,Karin Loser,Cord Sunderkötter,Thomas A. Luger,Carsten Weishaupt +9 more
TL;DR: In vitro assays showed that melanoma cells attach to NETs via integrin‐mediated adhesion and that NETs inhibit tumor cell migration, and discovered in vitro an antineoplastic role of NETs in melanoma.
Journal ArticleDOI
Integrin-dependent cell adhesion to neutrophil extracellular traps through engagement of fibronectin in neutrophil-like cells.
Marcello Monti,Francesca Iommelli,Viviana De Rosa,Maria Vincenza Carriero,Roberta Miceli,Rosa Camerlingo,Giovanni Di Minno,Silvana Del Vecchio +7 more
TL;DR: It is shown that α5β1 and ανβ3 integrins mediate cell adhesion to NETs by binding to their common substrate fibronectin.
Journal ArticleDOI
Circulating tumor cells in clinical research and monitoring patients with colorectal cancer.
Claudia Burz,Vlad-Vasile Pop,Rares Buiga,Sur Daniel,Gabriel Samasca,Cornel Aldea,Iulia Lupan +6 more
TL;DR: This review highlights the implication of circulating tumor cells in metastasis cascade, intrinsic tumor cells mechanisms and correlations with clinical parameters along with their utility for medical practice and detection techniques.
Journal ArticleDOI
The Dual Role of Myeloperoxidase in Immune Response.
TL;DR: This review critically reflects on the beneficial and harmful functions of MPO against the background of immune response.
Journal ArticleDOI
Mechanisms and disease relevance of neutrophil extracellular trap formation.
Kristof Van Avondt,Dominik Hartl +1 more
TL;DR: Current concepts of the mechanisms and disease relevance of NET formation are discussed and the disease relevance and clinical translatability of this unconventional cellular mechanism are discussed.
References
More filters
Journal ArticleDOI
Global cancer statistics, 2002.
TL;DR: There are striking variations in the risk of different cancers by geographic area, most of the international variation is due to exposure to known or suspected risk factors related to lifestyle or environment, and provides a clear challenge to prevention.
Journal ArticleDOI
Cancer statistics, 2013
TL;DR: Overall cancer death rates have declined 20% from their peak in 1991 to 2009 and can be accelerated by applying existing cancer control knowledge across all segments of the population, with an emphasis on those groups in the lowest socioeconomic bracket and other underserved populations.
Journal ArticleDOI
Neutrophil extracellular traps kill bacteria
Volker Brinkmann,Ulrike Reichard,Christian Goosmann,Beatrix Fauler,Yvonne Uhlemann,David S. Weiss,Yvette Weinrauch,Yvette Weinrauch,Arturo Zychlinsky +8 more
TL;DR: It is described that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria, which degrade virulence factors and kill bacteria.
Journal ArticleDOI
Revisions in the International System for Staging Lung Cancer
TL;DR: Analysis of a collected database representing all clinical, surgical-pathologic, and follow-up information for 5,319 patients treated for primary lung cancer confirmed the validity of the TNM and stage grouping classification schema.
Journal ArticleDOI
Preoperative Chemoradiotherapy for Esophageal or Junctional Cancer
TL;DR: Preoperative chemoradiotherapy improved survival among patients with potentially curable esophageal or esophagogastric-junction cancer and the regimen was associated with acceptable adverse-event rates.