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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Neutrophil: A New Player in Metastatic Cancers.
TL;DR: The current understanding of the role of neutrophils in cancer development is reviewed, with a specific focus on their pro-metastatic functions.
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The influence of the pre-metastatic niche on breast cancer metastasis.
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The Immune Microenvironment and Cancer Metastasis.
TL;DR: Understanding how disseminated tumor cells evade and corrupt the immune system during the final stages of metastasis will be pivotal in developing new therapeutic modalities that combat metastasis.
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Gram negative bacteria increase non-small cell lung cancer metastasis via Toll-like receptor 4 activation and mitogen-activated protein kinase phosphorylation.
Simon C. Chow,Stephen Gowing,Jonathan Cools-Lartigue,Crystal B. Chen,Julie Bérubé,Hee-Won Yoon,Carlos H. F. Chan,Mathieu Rousseau,Betty Giannias,Lucie Roussel,Salman T. Qureshi,Simon Rousseau,Lorenzo E. Ferri +12 more
TL;DR: It is demonstrated that NSCLC cells have increased in vivo adhesion to hepatic sinusoids after coincubation with gram negative bacteria, and TLR4 represents a potential therapeutic target to help prevent severe postoperative infection driven cancer metastasis.
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