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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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.
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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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Neutrophil Elastase Enhances Sputum Solubilization in Cystic Fibrosis Patients Receiving DNase Therapy
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Shahid Farid,Amer Aldouri,Gareth Morris-Stiff,Aamir Z. Khan,Giles J. Toogood,J. Peter A. Lodge,K. Rajendra Prasad +6 more
TL;DR: Thorough preoperative optimization, meticulous surgical technique and careful management in the postoperative period may reduce the incidence of postoperative complications and influence long-term outcomes in hepatic resection for CRLM.
Journal ArticleDOI
Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms
Braedon McDonald,Jonathan Spicer,Betty Giannais,Lucia Fallavollita,Pnina Brodt,Lorenzo E. Ferri +5 more
TL;DR: Disrupting the interactions between endothelial selectins and tumor cell selectin ligands diminished tumor cell recruitment to the liver and interactions between adherent neutrophils within the inflamed sinusoids and circulating tumor cells may further increase tumor cell arrest in the liver are shown.