Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Breast Cancer Research
Published in: Breast Cancer Research 1/2019

Open Access 01-12-2019 | Metastasis | Review

Neutrophil extracellular traps in breast cancer and beyond: current perspectives on NET stimuli, thrombosis and metastasis, and clinical utility for diagnosis and treatment

Authors: Hunter T. Snoderly, Brian A. Boone, Margaret F. Bennewitz

Published in: Breast Cancer Research | Issue 1/2019

Login to get access

Abstract

The formation of neutrophil extracellular traps (NETs), known as NETosis, was first observed as a novel immune response to bacterial infection, but has since been found to occur abnormally in a variety of other inflammatory disease states including cancer. Breast cancer is the most commonly diagnosed malignancy in women. In breast cancer, NETosis has been linked to increased disease progression, metastasis, and complications such as venous thromboembolism. NET-targeted therapies have shown success in preclinical cancer models and may prove valuable clinical targets in slowing or halting tumor progression in breast cancer patients. We will briefly outline the mechanisms by which NETs may form in the tumor microenvironment and circulation, including the crosstalk between neutrophils, tumor cells, endothelial cells, and platelets as well as the role of cancer-associated extracellular vesicles in modulating neutrophil behavior and NET extrusion. The prognostic implications of cancer-associated NETosis will be explored in addition to development of novel therapeutics aimed at targeting NET interactions to improve outcomes in patients with breast cancer.
Literature
1.
Kobayashi SD, Voyich JM, Burlak C, DeLeo FR. Neutrophils in the innate immune response. Archivum Immunologiae ET Therapiae Experimentalis-English Edition. 2005;53(6):505.
2.
Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303(5663):1532–5.PubMedCrossRef
3.
Yipp BG, Kubes P. NETosis: how vital is it? Blood J Am Soc Hematol. 2013;122(16):2784–94.
4.
Chowdhury CS, Giaglis S, Walker UA, Buser A, Hahn S, Hasler P. Enhanced neutrophil extracellular trap generation in rheumatoid arthritis: analysis of underlying signal transduction pathways and potential diagnostic utility. Arthritis Res Ther. 2014;16(3):R122.CrossRef
5.
Gupta AK, Hasler P, Holzgreve W, Gebhardt S, Hahn S. Induction of neutrophil extracellular DNA lattices by placental microparticles and IL-8 and their presence in preeclampsia. Hum Immunol. 2005;66(11):1146–54.PubMedCrossRef
6.
7.
Jorch SK, Kubes P. An emerging role for neutrophil extracellular traps in noninfectious disease. Nat Med. 2017;23(3):279.PubMedCrossRef
8.
Mitroulis I, Kambas K, Chrysanthopoulou A, Skendros P, Apostolidou E, Kourtzelis I, et al. Neutrophil extracellular trap formation is associated with IL-1β and autophagy-related signaling in gout. PLoS One. 2011;6(12):e29318.PubMedPubMedCentralCrossRef
9.
Wang Y, Xiao Y, Zhong L, Ye D, Zhang J, Tu Y, et al. Increased neutrophil elastase and proteinase 3 and augmented NETosis are closely associated with β-cell autoimmunity in patients with type 1 diabetes. Diabetes. 2014;63(12):4239–48.PubMedCrossRef
10.
Cools-Lartigue J, Spicer J, McDonald B, Gowing S, Chow S, Giannias B, et al. Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J Clin Invest. 2013;123(8):3446–58.PubMedCentralCrossRef
11.
Spicer JD, McDonald B, Cools-Lartigue JJ, Chow SC, Giannias B, Kubes P, et al. Neutrophils promote liver metastasis via mac-1-mediated interactions with circulating tumor cells. Cancer Res. 2012;72(16):3919–27.PubMedCrossRef
12.
Pieterse E, Rother N, Garsen M, Hofstra JM, Satchell SC, Hoffmann M, et al. Neutrophil extracellular traps drive endothelial-to-Mesenchymal transition. Arterioscler Thromb Vasc Biol. 2017;37(7):1371–9.PubMedCrossRef
13.
Albrengues J, Shields MA, Ng D, Park CG, Ambrico A, Poindexter ME, et al. Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science. 2018;361(6409):eaao4227.PubMedPubMedCentralCrossRef
14.
Tohme S, Yazdani HO, Al-Khafaji AB, Chidi AP, Loughran P, Mowen K, et al. Neutrophil extracellular traps promote the development and progression of liver metastases after surgical stress. Cancer Res. 2016;76(6):1367–80.PubMedPubMedCentralCrossRef
15.
Al-Haidari AA, Algethami N, Lepsenyi M, Rahman M, Syk I, Thorlacius H. Neutrophil extracellular traps promote peritoneal metastasis of colon cancer cells. Oncotarget. 2019;10(12):1238–49.PubMedPubMedCentralCrossRef
16.
Kanamaru R, Ohzawa H, Miyato H, Matsumoto S, Haruta H, Kurashina K, et al. Low density neutrophils (LDN) in postoperative abdominal cavity assist the peritoneal recurrence through the production of neutrophil extracellular traps (NETs). Sci Rep. 2018;8(1):632.PubMedPubMedCentralCrossRef
17.
Boone BA, Murthy P, Miller-Ocuin J, Doerfler WR, Ellis JT, Liang X, et al. Chloroquine reduces hypercoagulability in pancreatic cancer through inhibition of neutrophil extracellular traps. BMC Cancer. 2018;18(1):678.PubMedPubMedCentralCrossRef
18.
19.
Demers M, Krause DS, Schatzberg D, Martinod K, Voorhees JR, Fuchs TA, et al. Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis. Proc Natl Acad Sci U S A. 2012;109(32):13076–81.PubMedPubMedCentralCrossRef
20.
21.
Leal AC, Mizurini DM, Gomes T, Rochael NC, Saraiva EM, Dias MS, et al. Tumor-derived exosomes induce the formation of neutrophil extracellular traps: implications for the establishment of cancer-associated thrombosis. Sci Rep. 2017;7(1):6438.PubMedPubMedCentralCrossRef
22.
Arelaki S, Arampatzioglou A, Kambas K, Papagoras C, Miltiades P, Angelidou I, et al. Gradient infiltration of neutrophil extracellular traps in colon cancer and evidence for their involvement in tumour growth. PLoS One. 2016;11(5):e0154484.PubMedPubMedCentralCrossRef
23.
Demers M, Wong SL, Martinod K, Gallant M, Cabral JE, Wang Y, et al. Priming of neutrophils toward NETosis promotes tumor growth. Oncoimmunology. 2016;5(5):e1134073.PubMedPubMedCentralCrossRef
24.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.PubMedCrossRef
25.
Maugeri N, Campana L, Gavina M, Covino C, De Metrio M, Panciroli C, et al. Activated platelets present high mobility group box 1 to neutrophils, inducing autophagy and promoting the extrusion of neutrophil extracellular traps. J Thromb Haemost. 2014;12(12):2074–88.PubMedCrossRef
26.
Mauracher LM, Posch F, Martinod K, Grilz E, Däullary T, Hell L, et al. Citrullinated histone H3, a biomarker of neutrophil extracellular trap formation, predicts the risk of venous thromboembolism in cancer patients. J Thromb Haemost. 2018;16(3):508–18.PubMedPubMedCentralCrossRef
27.
Park J, Wysocki RW, Amoozgar Z, Maiorino L, Fein MR, Jorns J, et al. Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps. Sci Transl Med. 2016;8(361):361ra138.PubMedPubMedCentralCrossRef
28.
Saffarzadeh M, Juenemann C, Queisser MA, Lochnit G, Barreto G, Galuska SP, et al. Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones. PLoS One. 2012;7(2):e32366.PubMedPubMedCentralCrossRef
29.
Semeraro F, Ammollo CT, Morrissey JH, Dale GL, Friese P, Esmon NL, et al. Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and TLR4. Blood. 2011;118(7):1952–61.PubMedPubMedCentralCrossRef
30.
Ni P, Zhang Y, Liu Y, Lin X, Su X, Lu H, et al. HMGB1 silence could promote MCF-7 cell apoptosis and inhibit invasion and metastasis. Int J Clin Exp Pathol. 2015;8(12):15940.PubMedPubMedCentral
31.
Clark SR, Ma AC, Tavener SA, McDonald B, Goodarzi Z, Kelly MM, et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med. 2007;13(4):463.PubMedCrossRef
32.
Keshari RS, Verma A, Barthwal MK, Dikshit M. Reactive oxygen species-induced activation of ERK and p38 MAPK mediates PMA-induced NETs release from human neutrophils. J Cell Biochem. 2013;114(3):532–40.PubMedCrossRef
33.
Tadie J-M, Bae H-B, Jiang S, Park DW, Bell CP, Yang H, et al. HMGB1 promotes neutrophil extracellular trap formation through interactions with toll-like receptor 4. Am J Phys Lung Cell Mol Phys. 2013;304(5):L342–L9.
34.
Gupta AK, Joshi MB, Philippova M, Erne P, Hasler P, Hahn S, et al. Activated endothelial cells induce neutrophil extracellular traps and are susceptible to NETosis-mediated cell death. FEBS Lett. 2010;584(14):3193–7.PubMedCrossRef
35.
De Larco JE, Wuertz BR, Furcht LT. The potential role of neutrophils in promoting the metastatic phenotype of tumors releasing interleukin-8. Clin Cancer Res. 2004;10(15):4895–900.PubMedCrossRef
36.
Avalos BR, Gasson JC, Hedvat C, Quan S, Baldwin G, Weisbart R, et al. Human granulocyte colony-stimulating factor: biologic activities and receptor characterization on hematopoietic cells and small cell lung cancer cell lines. Blood. 1990;75(4):851–7.PubMedCrossRef
37.
Cedervall J, Zhang Y, Huang H, Zhang L, Femel J, Dimberg A, et al. Neutrophil extracellular traps accumulate in peripheral blood vessels and compromise organ function in tumor-bearing animals. Cancer Res. 2015;75(13):2653–62.PubMedCrossRef
38.
Li P, Li M, Lindberg MR, Kennett MJ, Xiong N, Wang Y. PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J Exp Med. 2010;207(9):1853–62.PubMedPubMedCentralCrossRef
39.
40.
Chang X, Han J, Pang L, Zhao Y, Yang Y, Shen Z. Increased PADI4 expression in blood and tissues of patients with malignant tumors. BMC Cancer. 2009;9(1):40.PubMedPubMedCentralCrossRef
41.
Etulain J, Martinod K, Wong SL, Cifuni SM, Schattner M, Wagner DD. P-selectin promotes neutrophil extracellular trap formation in mice. Blood. 2015;126(2):242–6.PubMedPubMedCentralCrossRef
42.
Kambas K, Chrysanthopoulou A, Vassilopoulos D, Apostolidou E, Skendros P, Girod A, et al. Tissue factor expression in neutrophil extracellular traps and neutrophil derived microparticles in antineutrophil cytoplasmic antibody associated vasculitis may promote thromboinflammation and the thrombophilic state associated with the disease. Ann Rheum Dis. 2014;73(10):1854–63.PubMedCrossRef
43.
Stakos DA, Kambas K, Konstantinidis T, Mitroulis I, Apostolidou E, Arelaki S, et al. Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction. Eur Heart J. 2015;36(22):1405–14.PubMedPubMedCentralCrossRef
44.
Ruf W, Yokota N, Schaffner F. Tissue factor in cancer progression and angiogenesis. Thromb Res. 2010;125:S36–S8.PubMedCrossRef
45.
Kirchner T, Möller S, Klinger M, Solbach W, Laskay T, Behnen M. The impact of various reactive oxygen species on the formation of neutrophil extracellular traps. Mediat Inflamm. 2012;2012.
46.
Warnatsch A, Tsourouktsoglou T-D, Branzk N, Wang Q, Reincke S, Herbst S, et al. Reactive oxygen species localization programs inflammation to clear microbes of different size. Immunity. 2017;46(3):421–32.PubMedPubMedCentralCrossRef
47.
Davidson B, Konstantinovsky S, Kleinberg L, Nguyen MT, Bassarova A, Kvalheim G, et al. The mitogen-activated protein kinases (MAPK) p38 and JNK are markers of tumor progression in breast carcinoma. Gynecol Oncol. 2006;102(3):453–61.PubMedCrossRef
48.
Zhao M, Howard EW, Parris AB, Guo Z, Zhao Q, Yang X. Alcohol promotes migration and invasion of triple-negative breast cancer cells through activation of p38 MAPK and JNK. Mol Carcinog. 2017;56(3):849–62.PubMedCrossRef
49.
Rochael NC, Guimarães-Costa AB, Nascimento MT, DeSouza-Vieira TS, Oliveira MP, e Souza LFG, et al. Classical ROS-dependent and early/rapid ROS-independent release of neutrophil extracellular traps triggered by Leishmania parasites. Scientific Reports 2015;5:18302.
50.
Wang Y, Li M, Stadler S, Correll S, Li P, Wang D, et al. Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J Cell Biol. 2009;184(2):205–13.PubMedPubMedCentralCrossRef
51.
52.
Papayannopoulos V, Metzler KD, Hakkim A, Zychlinsky A. Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J Cell Biol. 2010;191(3):677–91.PubMedPubMedCentralCrossRef
53.
Kwak T, Drews-Elger K, Ergonul A, Miller PC, Braley A, Hwang GH, et al. Targeting of RAGE-ligand signaling impairs breast cancer cell invasion and metastasis. Oncogene. 2017;36(11):1559–72.PubMedCrossRef
54.
Boone BA, Orlichenko L, Schapiro NE, Loughran P, Gianfrate GC, Ellis JT, et al. The receptor for advanced glycation end products (RAGE) enhances autophagy and neutrophil extracellular traps in pancreatic cancer. Cancer Gene Ther. 2015;22(6):326–34.PubMedPubMedCentralCrossRef
55.
Kang R, Tang D, Lotze MT, Zeh HJ, 3rd. RAGE regulates autophagy and apoptosis following oxidative injury. Autophagy. 2011;7(4):442–4.
56.
Pham DL, Ban GY, Kim SH, Shin YS, Ye YM, Chwae YJ, et al. Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma. Clin Exp Allergy. 2017;47(1):57–70.PubMedCrossRef
57.
Sha LL, Wang H, Wang C, Peng HY, Chen M, Zhao MH. Autophagy is induced by anti-neutrophil cytoplasmic Abs and promotes neutrophil extracellular traps formation. Innate Immun. 2016;22(8):658–65.PubMedCrossRef
58.
Park SY, Shrestha S, Youn YJ, Kim JK, Kim SY, Kim HJ, et al. Autophagy primes neutrophils for neutrophil extracellular trap formation during Sepsis. Am J Respir Crit Care Med. 2017;196(5):577–89.PubMedCrossRef
59.
Remijsen Q, Vanden Berghe T, Wirawan E, Asselbergh B, Parthoens E, De Rycke R, et al. Neutrophil extracellular trap cell death requires both autophagy and superoxide generation. Cell Res. 2011;21(2):290–304.PubMedCrossRef
60.
Amulic B, Knackstedt SL, Abed UA, Deigendesch N, Harbort CJ, Caffrey BE, et al. Cell-cycle proteins control production of neutrophil extracellular traps. Developmental Cell. 2017;43(4):449–62 e5.PubMedCrossRef
61.
Lukášová E, Kořistek Z, Klabusay M, Ondřej V, Grigoryev S, Bačíková A, et al. Granulocyte maturation determines ability to release chromatin NETs and loss of DNA damage response; these properties are absent in immature AML granulocytes. Biochimica et Biophysica Acta (BBA)-molecular. Cell Res. 2013;1833(3):767–79.
62.
Mackey JBG, Coffelt SB, Carlin LM. Neutrophil Maturity in Cancer. Frontiers in Immunology. 2019;10(1912).
63.
Powell DR, Huttenlocher A. Neutrophils in the tumor microenvironment. Trends Immunol. 2016;37(1):41–52.PubMedCrossRef
64.
Hunter KW Jr. Murine mammary carcinoma 4T1 induces a leukemoid reaction with splenomegaly: association with tumor-derived growth factors. Exp Mol Pathol. 2007;82(1):12–24.PubMedCrossRef
65.
Kowanetz M, Wu X, Lee J, Tan M, Hagenbeek T, Qu X, et al. Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+ Ly6C+ granulocytes. Proc Natl Acad Sci. 2010;107(50):21248–55.PubMedCrossRefPubMedCentral
66.
Sugimoto C, Fujieda S, Sunaga H, Noda I, Tanaka N, Kimura Y, et al. Granulocyte colony-stimulating factor (G-CSF)-mediated signaling regulates type IV collagenase activity in head and neck cancer cells. Int J Cancer. 2001;93(1):42–6.PubMedCrossRef
67.
de Oliveira S, Reyes-Aldasoro CC, Candel S, Renshaw SA, Mulero V, Calado Â. Cxcl8 (IL-8) mediates neutrophil recruitment and behavior in the zebrafish inflammatory response. J Immunol. 2013;190(8):4349–59.PubMedCrossRef
68.
Kozłowski L, Zakrzewska I, Tokajuk P, Wojtukiewicz M. Concentration of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10) in blood serum of breast cancer patients. Roczniki Akademii Medycznej w Bialymstoku (1995). 2003;48:82–4.
69.
Xu R, Bao C, Huang H, Lin F, Yuan Y, Wang S, et al. Low expression of CXCR1/2 on neutrophils predicts poor survival in patients with hepatitis B virus-related acute-on-chronic liver failure. Sci Rep. 2016;6:38714.PubMedPubMedCentralCrossRef
70.
Alfaro C, Teijeira A, Oñate C, Pérez G, Sanmamed MF, Andueza MP, et al. Tumor-produced interleukin-8 attracts human myeloid-derived suppressor cells and elicits extrusion of neutrophil extracellular traps (NETs). Clin Cancer Res. 2016;22(15):3924–36.PubMedCrossRef
71.
Jin L, Batra S, Douda DN, Palaniyar N, Jeyaseelan S. CXCL1 contributes to host defense in polymicrobial sepsis via modulating T cell and neutrophil functions. J Immunol. 2014;193(7):3549–58.PubMedCrossRef
72.
Jin L, Batra S, Jeyaseelan S. Diminished neutrophil extracellular trap (NET) formation is a novel innate immune deficiency induced by acute ethanol exposure in polymicrobial sepsis, which can be rescued by CXCL1. PLoS Pathog. 2017;13(9):e1006637.PubMedPubMedCentralCrossRef
73.
Jeannin P, Delneste Y, Gosset P, Molet S, Lassalle P, Hamid Q, et al. Histamine induces interleukin-8 secretion by endothelial cells. Blood. 1994;84(7):2229–33.PubMedCrossRef
74.
75.
Corre I, Paris F, Huot J. The p38 pathway, a major pleiotropic cascade that transduces stress and metastatic signals in endothelial cells. Oncotarget. 2017;8(33):55684.PubMedPubMedCentralCrossRef
76.
Schreiber A, Rousselle A, Becker JU, von Mässenhausen A, Linkermann A, Kettritz R. Necroptosis controls NET generation and mediates complement activation, endothelial damage, and autoimmune vasculitis. Proc Natl Acad Sci. 2017;114(45):E9618–E25.PubMedCrossRefPubMedCentral
77.
Knight JS, Luo W, O’Dell AA, Yalavarthi S, Zhao W, Subramanian V, et al. Peptidylarginine deiminase inhibition reduces vascular damage and modulates innate immune responses in murine models of atherosclerosis. Circ Res. 2014;114(6):947–56.PubMedPubMedCentralCrossRef
78.
Goerge T, Barg A, Schnaeker E-M, Poppelmann B, Shpacovitch V, Rattenholl A, et al. Tumor-derived matrix metalloproteinase-1 targets endothelial proteinase-activated receptor 1 promoting endothelial cell activation. Cancer Res. 2006;66(15):7766–74.PubMedCrossRef
79.
Andrews RK, Arthur JF, Gardiner EE. Neutrophil extracellular traps (NETs) and the role of platelets in infection. Thromb Haemost. 2014;112(10):659–65.PubMedCrossRef
80.
Ueno T, Toi M, Koike M, Nakamura S, Tominaga T. Tissue factor expression in breast cancer tissues: its correlation with prognosis and plasma concentration. Br J Cancer. 2000;83(2):164.PubMedPubMedCentralCrossRef
81.
Pabinger I, Thaler J, Ay C. Biomarkers for prediction of venous thromboembolism in cancer. Blood. 2013;122(12):2011–8.PubMedCrossRef
82.
Abdol Razak N, Elaskalani O, Metharom P. Pancreatic cancer-induced neutrophil extracellular traps: a potential contributor to cancer-associated thrombosis. Int J Mol Sci. 2017;18(3):487.PubMedCentralCrossRef
83.
Ma A, Kubes P. Platelets, neutrophils, and neutrophil extracellular traps (NETs) in sepsis. J Thromb Haemost. 2008;6(3):415–20.PubMedCrossRef
84.
Li J, Kim K, Hahm E, Molokie R, Hay N, Gordeuk VR, et al. Neutrophil AKT2 regulates heterotypic cell-cell interactions during vascular inflammation. J Clin Invest. 2014;124(4):1483–96.PubMedPubMedCentralCrossRef
85.
Sreeramkumar V, Adrover JM, Ballesteros I, Cuartero MI, Rossaint J, Bilbao I, et al. Neutrophils scan for activated platelets to initiate inflammation. Science. 2014;346(6214):1234–8.PubMedPubMedCentralCrossRef
86.
Nagata K, Tsuji T, Todoroki N, Katagiri Y, Tanoue K, Yamazaki H, et al. Activated platelets induce superoxide anion release by monocytes and neutrophils through P-selectin (CD62). J Immunol. 1993;151(6):3267–73.PubMed
87.
Ay C, Simanek R, Vormittag R, Dunkler D, Alguel G, Koder S, et al. High plasma levels of soluble P-selectin are predictive of venous thromboembolism in cancer patients: results from the Vienna Cancer and thrombosis study (CATS). Blood. 2008;112(7):2703–8.PubMedCrossRef
88.
Zomer A, Maynard C, Verweij FJ, Kamermans A, Schafer R, Beerling E, et al. In vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior. Cell. 2015;161(5):1046–57.PubMedPubMedCentralCrossRef
89.
Akers JC, Gonda D, Kim R, Carter BS, Chen CC. Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J Neuro-Oncol. 2013;113(1):1–11.CrossRef
90.
Xu R, Greening DW, Zhu H-J, Takahashi N, Simpson RJ. Extracellular vesicle isolation and characterization: toward clinical application. J Clin Invest. 2016;126(4):1152–62.PubMedPubMedCentralCrossRef
91.
König L, Kasimir-Bauer S, Bittner A-K, Hoffmann O, Wagner B, Santos Manvailer LF, et al. Elevated levels of extracellular vesicles are associated with therapy failure and disease progression in breast cancer patients undergoing neoadjuvant chemotherapy. Oncoimmunology. 2018;7(1):e1376153.CrossRef
92.
Becker A, Thakur BK, Weiss JM, Kim HS, Peinado H, Lyden D. Extracellular vesicles in cancer: cell-to-cell mediators of metastasis. Cancer Cell. 2016;30(6):836–48.PubMedPubMedCentralCrossRef
93.
Chen I-H, Xue L, Hsu C-C, Paez JSP, Pan L, Andaluz H, et al. Phosphoproteins in extracellular vesicles as candidate markers for breast cancer. Proc Natl Acad Sci. 2017;114(12):3175–80.PubMedCrossRefPubMedCentral
94.
Logozzi M, De Milito A, Lugini L, Borghi M, Calabro L, Spada M, et al. High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients. PLoS One. 2009;4(4):e5219.PubMedPubMedCentralCrossRef
95.
Headley MB, Bins A, Nip A, Roberts EW, Looney MR, Gerard A, et al. Visualization of immediate immune responses to pioneer metastatic cells in the lung. Nature. 2016;531(7595):513.PubMedPubMedCentralCrossRef
96.
Chennakrishnaiah S, Meehan B, D'Asti E, Montermini L, Lee TH, Karatzas N, et al. Leukocytes as a reservoir of circulating oncogenic DNA and regulatory targets of tumor-derived extracellular vesicles. J Thromb Haemost. 2018;16(9):1800–13.PubMedCrossRef
97.
Walker AJ, West J, Card TR, Crooks C, Kirwan CC, Grainge MJ. When are breast cancer patients at highest risk of venous thromboembolism? A cohort study using English health care data. Blood. 2016;127(7):849–57.PubMedPubMedCentralCrossRef
98.
Agassi R, Czeiger D, Shaked G, Avriel A, Sheynin J, Lavrenkov K, et al. Measurement of circulating cell-free DNA levels by a simple fluorescent test in patients with breast cancer. Am J Clin Pathol. 2015;143(1):18–24.PubMedCrossRef
99.
Czeiger D, Shaked G, Eini H, Vered I, Belochitski O, Avriel A, et al. Measurement of circulating cell-free DNA levels by a new simple fluorescent test in patients with primary colorectal cancer. Am J Clin Pathol. 2011;135(2):264–70.PubMedCrossRef
100.
Kohler C, Radpour R, Barekati Z, Asadollahi R, Bitzer J, Wight E, et al. Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors. Mol Cancer. 2009;8(1):105.PubMedPubMedCentralCrossRef
101.
Yoo DG, Floyd M, Winn M, Moskowitz SM, Rada B. NET formation induced by Pseudomonas aeruginosa cystic fibrosis isolates measured as release of myeloperoxidase-DNA and neutrophil elastase-DNA complexes. Immunol Lett. 2014;160(2):186–94.PubMedCrossRef
102.
Thålin C, Lundström S, Seignez C, Daleskog M, Lundström A, Henriksson P, et al. Citrullinated histone H3 as a novel prognostic blood marker in patients with advanced cancer. PLoS One. 2018;13(1):e0191231.PubMedPubMedCentralCrossRef
103.
Trejo-Becerril C, Pérez-Cardenas E, Gutiérrez-Díaz B, De La Cruz-Sigüenza D, Taja-Chayeb L, González-Ballesteros M, et al. Antitumor effects of systemic DNAse I and proteases in an in vivo model. Integr Cancer Ther. 2016;15(4):NP35–43.PubMedPubMedCentralCrossRef
104.
Jones J, Causey C, Knuckley B, Slack-Noyes JL, Thompson PR. Protein arginine deiminase 4 (PAD4): current understanding and future therapeutic potential. Curr Opin Drug Discov Devel. 2009;12(5):616.PubMedPubMedCentral
105.
Lewis HD, Liddle J, Coote JE, Atkinson SJ, Barker MD, Bax BD, et al. Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation. Nat Chem Biol. 2015;11(3):189.PubMedPubMedCentralCrossRef
106.
Cedervall J, Dragomir A, Saupe F, Zhang Y, Arnlov J, Larsson E, et al. Pharmacological targeting of peptidylarginine deiminase 4 prevents cancer-associated kidney injury in mice. Oncoimmunol. 2017;6(8):e1320009.CrossRef
107.
Yazdani HO, Roy E, Comerci AJ, van der Windt DJ, Zhang H, Huang H, et al. Neutrophil extracellular traps drive mitochondrial homeostasis in tumors to augment growth. Cancer Research. 2019:canres. 0800.2019.
108.
Ataga KI, Kutlar A, Kanter J, Liles D, Cancado R, Friedrisch J, et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 2017;376(5):429–39.PubMedCrossRef
109.
Lapponi MJ, Carestia A, Landoni VI, Rivadeneyra L, Etulain J, Negrotto S, et al. Regulation of neutrophil extracellular trap formation by anti-inflammatory drugs. J Pharmacol Exp Ther. 2013;345(3):430–7.PubMedCrossRef
110.
Rothwell PM, Wilson M, Price JF, Belch JF, Meade TW, Mehta Z. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet. 2012;379(9826):1591–601.PubMedCrossRef
111.
112.
Murthy P, Singhi AD, Ross MA, Loughran P, Paragomi P, Papachristou GI, et al. Enhanced neutrophil extracellular trap formation in acute pancreatitis contributes to disease severity and is reduced by chloroquine. Front Immunol. 2019;10:28.PubMedPubMedCentralCrossRef
113.
Cook KL, Warri A, Soto-Pantoja DR, Clarke PA, Cruz MI, Zwart A, et al. Hydroxychloroquine inhibits autophagy to potentiate antiestrogen responsiveness in ER+ breast cancer. Clin Cancer Res. 2014;20(12):3222–32.PubMedPubMedCentralCrossRef
114.
Wolpin BM, Rubinson DA, Wang X, Chan JA, Cleary JM, Enzinger PC, et al. Phase II and pharmacodynamic study of autophagy inhibition using hydroxychloroquine in patients with metastatic pancreatic adenocarcinoma. Oncologist. 2014;19(6):637–8.PubMedPubMedCentralCrossRef
115.
Boone BA, Bahary N, Zureikat AH, Moser AJ, Normolle DP, Wu WC, et al. Safety and biologic response of pre-operative autophagy inhibition in combination with gemcitabine in patients with pancreatic adenocarcinoma. Ann Surg Oncol. 2015;22(13):4402–10.PubMedPubMedCentralCrossRef
116.
Labro M, Babin-Chevaye C. Effects of amodiaquine, chloroquine, and mefloquine on human polymorphonuclear neutrophil function in vitro. Antimicrob Agents Chemother. 1988;32(8):1124–30.PubMedPubMedCentralCrossRef
Metadata
Title
Neutrophil extracellular traps in breast cancer and beyond: current perspectives on NET stimuli, thrombosis and metastasis, and clinical utility for diagnosis and treatment
Authors
Hunter T. Snoderly
Brian A. Boone
Margaret F. Bennewitz
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2019
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-019-1237-6

Other articles of this Issue 1/2019

Breast Cancer Research 1/2019 Go to the issue

Research article

The opposing effects of interferon-beta and oncostatin-M as regulators of cancer stem cell plasticity in triple-negative breast cancer

Research article

Development of central nervous system metastases as a first site of metastatic disease in breast cancer patients treated in the neoadjuvant trials GeparQuinto and GeparSixto

Research article

Development of clinically relevant in vivo metastasis models using human bone discs and breast cancer patient-derived xenografts

Research article

Methylglyoxal, a glycolysis metabolite, triggers metastasis through MEK/ERK/SMAD1 pathway activation in breast cancer

Research article

Radiomic signatures with contrast-enhanced magnetic resonance imaging for the assessment of breast cancer receptor status and molecular subtypes: initial results

Research article

CGRRF1, a growth suppressor, regulates EGFR ubiquitination in breast cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits