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
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.
Journal ArticleDOI
The Cancer Stem Cell Niche: How Essential Is the Niche in Regulating Stemness of Tumor Cells?
Vicki Plaks,Niwen Kong,Zena Werb +2 more
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
More filters
Journal ArticleDOI
Tissue resident stem cells produce CCL5 under the influence of cancer cells and thereby promote breast cancer cell invasion.
Severin Pinilla,Eckhard Alt,F.J. Abdul Khalek,Constantin Jotzu,Fabian Muehlberg,Christoph Beckmann,Yao-Hua Song +6 more
TL;DR: It is concluded that CCL5 plays a crucial role for tumor invasion in the interplay of tissue resident stem cells from the fat tissue and breast cancer cells.
Journal ArticleDOI
Role of the hemopexin domain of matrix metalloproteinases in cell migration
TL;DR: It is demonstrated that MMPs utilize a non‐proteolytic mechanism to enhance epithelial cell migration and proposed that hemopexin homodimer formation is required for the full cell migratory function of proMMP‐9.
Journal ArticleDOI
G-protein-coupled receptor signaling in Syk-deficient neutrophils and mast cells
Attila Mócsai,Hong Zhang,Hong Zhang,Hong Zhang,Zoltán Jakus,Zoltán Jakus,Zoltán Jakus,Jiro Kitaura,Jiro Kitaura,Jiro Kitaura,Toshiaki Kawakami,Toshiaki Kawakami,Toshiaki Kawakami,Clifford A. Lowell +13 more
TL;DR: It is shown that Syk does not play a major functional role in chemoattractant/chemokine signaling in neutrophils and mast cells and that bone marrow-derived syk(-/-) mast cells showed normal activation of the Akt, ERK, and p38 MAP kinase pathways when stimulated by the GPCR ligand adenosine.
Journal Article
Pretreatment Neutrophil:Lymphocyte Ratio as a Prognostic Factor in Cervical Carcinoma
Yoo-Young Lee,Chel Hun Choi,Ha-Jeong Kim,Tae-Joong Kim,Jeong-Won Lee,Je-Ho Lee,Duk-Soo Bae,Byoung-Gie Kim +7 more
TL;DR: Pretreatment NLR may be a cost-effective biomarker to stratify risk of recurrence and death in patients with cervical cancer.
Journal ArticleDOI
Neutrophils influence melanoma adhesion and migration under flow conditions.
Margaret J. Slattery,Cheng Dong +1 more
TL;DR: The results suggest that transmigration of C8161 cells under flow conditions can be influenced by PMNs, mediated by Mac‐1/ICAM‐1 adhesive interactions and enhanced by altered cytokine production.