{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T13:42:17Z","timestamp":1794490937139,"version":"4.9.1"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004027","name":"Postdoctoral Foundation of Hei Long Jiang Province","doi-asserted-by":"publisher","award":["LBH-Q16219"],"award-info":[{"award-number":["LBH-Q16219"]}],"id":[{"id":"10.13039\/501100004027","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Excellent Scientific Research Team Project of the First Affiliated Hospital of Jiamusi University","award":["202301"],"award-info":[{"award-number":["202301"]}],"id":[{"id":"https:\/\/ror.org\/01djnt473","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Research Projects of Basic Scientific Research Business Expenses of Provincial Colleges and Universities in Heilongjiang Province","award":["2022-KYYWF-0627"],"award-info":[{"award-number":["2022-KYYWF-0627"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Inflammation-related predisposition to cancer plays an essential role in cancer progression and is associated with poor prognosis. A hypoxic microenvironment and neutrophil infiltration are commonly present in solid tumours, including gastric cancer (GC). Neutrophil extracellular traps (NETs) have also been demonstrated in the tumour immune microenvironment (TIME), but how NETs affect GC progression remains unknown. Here, we investigated the role of NET formation in the TIME and further explored the underlying mechanism of NETs in GC tumour growth.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Hypoxia-induced factor-1\u03b1 (HIF-1\u03b1), citrulline histone 3 (citH3) and CD66b expression in tumour and adjacent nontumor tissue samples was evaluated by western blotting, immunofluorescence and immunohistochemical staining. The expression of neutrophil-attracting chemokines in GC cells and their hypoxic-CM was measured by qRT\u2012PCR and ELISA. Neutrophil migration under hypoxic conditions was evaluated by a Transwell assay. Pathway activation in neutrophils in a hypoxic microenvironment were analysed by western blotting. NET formation was measured in vitro by immunofluorescence staining. The protumour effect of NETs on GC cells was identified by Transwell, wound healing and cell proliferation assays. In vivo, an lipopolysaccharide (LPS)-induced NET model and subcutaneous tumour model were established in BALB\/c nude mice to explore the mechanism of NETs in tumour growth.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GC generates a hypoxic microenvironment that recruits neutrophils and induces NET formation. High mobility group box 1 (HMGB1) was translocated to the cytoplasm from the nucleus of GC cells in the hypoxic microenvironment and mediated the formation of NETs via the toll-like receptor 4 (TLR4)\/p38 MAPK signalling pathway in neutrophils. HMGB1\/TLR4\/p38 MAPK pathway inhibition abrogated hypoxia-induced neutrophil activation and NET formation. NETs directly induced GC cell invasion and migration but not proliferation and accelerated the augmentation of GC growth by increasing angiogenesis. This rapid tumour growth was abolished by treatment with the NET inhibitor deoxyribonuclease I (DNase I) or a p38 MAPK signalling pathway inhibitor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Hypoxia triggers an inflammatory response and NET formation in the GC TIME to augment tumour growth. Targeting NETs with DNase I or HMGB1\/TLR4\/p38 MAPK pathway inhibitors is a potential therapeutic strategy to inhibit GC progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12964-023-01112-5","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T10:01:29Z","timestamp":1682935289000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":105,"title":["Neutrophil extracellular traps induced by the hypoxic microenvironment in gastric cancer augment tumour growth"],"prefix":"10.1186","volume":"21","author":[{"given":"Jiacheng","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biying","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanbei","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehan","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingwang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwu","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fujun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shifeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoxin","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,5,1]]},"reference":[{"issue":"3","key":"1112_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clin. 2021;71(3):209\u201349.","journal-title":"CA: A Cancer J Clin"},{"issue":"1","key":"1112_CR2","first-page":"7","volume":"69","author":"R Siegel","year":"2019","unstructured":"Siegel R, Miller K, Jemal A. Cancer statistics, 2019. CA: A Cancer J Clin. 2019;69(1):7\u201334.","journal-title":"CA: A Cancer J Clin"},{"issue":"4","key":"1112_CR3","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1097\/CCO.0000000000000636","volume":"32","author":"E Saad","year":"2020","unstructured":"Saad E, Buyse M. Statistical aspects in adjuvant and neoadjuvant trials for gastrointestinal cancer in 2020: focus on time-to-event endpoints. Curr Opin Oncol. 2020;32(4):384\u201390.","journal-title":"Curr Opin Oncol"},{"issue":"3","key":"1112_CR4","first-page":"264","volume":"71","author":"S Joshi","year":"2021","unstructured":"Joshi S, Badgwell B. Current treatment and recent progress in gastric cancer. CA: A Cancer J Clin. 2021;71(3):264\u201379.","journal-title":"CA: A Cancer J Clin"},{"issue":"12","key":"1112_CR5","doi-asserted-by":"publisher","first-page":"1656","DOI":"10.1158\/2159-8290.CD-19-0487","volume":"9","author":"A Nagaraja","year":"2019","unstructured":"Nagaraja A, Kikuchi O, Bass A. Genomics and targeted therapies in gastroesophageal adenocarcinoma. Cancer Discov. 2019;9(12):1656\u201372.","journal-title":"Cancer Discov"},{"issue":"8","key":"1112_CR6","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/s41571-021-00492-2","volume":"18","author":"Y Nakamura","year":"2021","unstructured":"Nakamura Y, Kawazoe A, Lordick F, Janjigian Y, Shitara K. Biomarker-targeted therapies for advanced-stage gastric and gastro-oesophageal junction cancers: an emerging paradigm. Nat Rev Clin Oncol. 2021;18(8):473\u201387.","journal-title":"Nat Rev Clin Oncol"},{"issue":"6","key":"1112_CR7","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.cell.2010.01.025","volume":"140","author":"S Grivennikov","year":"2010","unstructured":"Grivennikov S, Greten F, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883\u201399.","journal-title":"Cell"},{"issue":"29","key":"1112_CR8","doi-asserted-by":"publisher","first-page":"4531","DOI":"10.1200\/JCO.2009.27.2146","volume":"28","author":"M Disis","year":"2010","unstructured":"Disis M. Immune regulation of cancer. J Clin Oncol\u202f: Official J Am Soc Clin Oncol. 2010;28(29):4531\u20138.","journal-title":"J Clin Oncol : Official J Am Soc Clin Oncol"},{"issue":"17","key":"1112_CR9","doi-asserted-by":"publisher","first-page":"4495","DOI":"10.3390\/cancers13174495","volume":"13","author":"U Demkow","year":"2021","unstructured":"Demkow U. Neutrophil Extracellular Traps (NETs) in cancer invasion, evasion and metastasis. Cancers (Basel). 2021;13(17):4495.","journal-title":"Cancers (Basel)"},{"issue":"21","key":"1112_CR10","doi-asserted-by":"publisher","first-page":"5626","DOI":"10.1158\/0008-5472.CAN-19-0800","volume":"79","author":"H Yazdani","year":"2019","unstructured":"Yazdani H, Roy E, Comerci A, van der Windt D, Zhang H, Huang H, et al. Neutrophil extracellular traps drive mitochondrial homeostasis in tumors to augment growth. Can Res. 2019;79(21):5626\u201339.","journal-title":"Can Res"},{"issue":"5663","key":"1112_CR11","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1126\/science.1092385","volume":"303","author":"V Brinkmann","year":"2004","unstructured":"Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss D, et al. Neutrophil extracellular traps kill bacteria. Science (New York, NY). 2004;303(5663):1532\u20135.","journal-title":"Science (New York, NY)"},{"issue":"6","key":"1112_CR12","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.3390\/cancers12061542","volume":"12","author":"K Martins-Cardoso","year":"2020","unstructured":"Martins-Cardoso K, Almeida V, Bagri K, Rossi M, Mermelstein C, K\u00f6nig S, et al. Neutrophil Extracellular Traps (NETs) promote pro-metastatic phenotype in human breast cancer cells through epithelial-mesenchymal transition. Cancers. 2020;12(6):1542.","journal-title":"Cancers"},{"key":"1112_CR13","doi-asserted-by":"publisher","first-page":"636954","DOI":"10.3389\/fimmu.2021.636954","volume":"12","author":"D Domer","year":"2021","unstructured":"Domer D, Walther T, Moller S, Behnen M, Laskay T. Neutrophil extracellular traps activate proinflammatory functions of human neutrophils. Front Immunol. 2021;12:636954.","journal-title":"Front Immunol"},{"issue":"8","key":"1112_CR14","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1161\/ATVBAHA.111.242859","volume":"32","author":"T Fuchs","year":"2012","unstructured":"Fuchs T, Brill A, Wagner D. Neutrophil extracellular trap (NET) impact on deep vein thrombosis. Arterioscler Thromb Vasc Biol. 2012;32(8):1777\u201383.","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"11","key":"1112_CR15","first-page":"14075","volume":"8","author":"C Yang","year":"2015","unstructured":"Yang C, Sun W, Cui W, Li X, Yao J, Jia X, et al. Procoagulant role of neutrophil extracellular traps in patients with gastric cancer. Int J Clin Exp Pathol. 2015;8(11):14075\u201386.","journal-title":"Int J Clin Exp Pathol"},{"issue":"1","key":"1112_CR16","doi-asserted-by":"publisher","first-page":"127","DOI":"10.3892\/ijmm.2021.4960","volume":"48","author":"T Zhu","year":"2021","unstructured":"Zhu T, Zou X, Yang C, Li L, Wang B, Li R, et al. Neutrophil extracellular traps promote gastric cancer metastasis by inducing epithelial-mesenchymal transition. Int J Mol Med. 2021;48(1):127.","journal-title":"Int J Mol Med"},{"key":"1112_CR17","doi-asserted-by":"publisher","first-page":"5271","DOI":"10.2147\/OTT.S227331","volume":"13","author":"R Li","year":"2020","unstructured":"Li R, Zou X, Zhu T, Xu H, Li X, Zhu L. Destruction of neutrophil extracellular traps promotes the apoptosis and inhibits the invasion of gastric cancer cells by regulating the expression of Bcl-2 Bax and NF-\u03baB. OncoTargets Ther. 2020;13:5271\u201381.","journal-title":"OncoTargets Ther"},{"issue":"26","key":"1112_CR18","doi-asserted-by":"publisher","first-page":"3132","DOI":"10.3748\/wjg.v28.i26.3132","volume":"28","author":"J Li","year":"2022","unstructured":"Li J, Zou X, Yang S, Jin J, Zhu L, Li C, et al. Neutrophil extracellular traps participate in the development of cancer-associated thrombosis in patients with gastric cancer. World J Gastroenterol. 2022;28(26):3132\u201349.","journal-title":"World J Gastroenterol"},{"issue":"6","key":"1112_CR19","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1158\/1078-0432.CCR-18-1226","volume":"25","author":"M Nie","year":"2019","unstructured":"Nie M, Yang L, Bi X, Wang Y, Sun P, Yang H, et al. Neutrophil Extracellular traps induced by il8 promote diffuse large B-cell lymphoma progression via the TLR9 signaling. Clin Cancer Res\u202f: An Official J Am Assoc Cancer Res. 2019;25(6):1867\u201379.","journal-title":"Clin Cancer Res : An Official J Am Assoc Cancer Res"},{"issue":"14","key":"1112_CR20","doi-asserted-by":"publisher","first-page":"7260","DOI":"10.3390\/ijms22147260","volume":"22","author":"U Khan","year":"2021","unstructured":"Khan U, Chowdhury S, Billah M, Islam K, Thorlacius H, Rahman M. Neutrophil extracellular traps in colorectal cancer progression and metastasis. Int J Mol Sci. 2021;22(14):7260.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"1112_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1152\/physrev.00018.2019","volume":"100","author":"C Riera-Domingo","year":"2020","unstructured":"Riera-Domingo C, Audig\u00e9 A, Granja S, Cheng W, Ho P, Baltazar F, et al. Immunity, hypoxia, and metabolism-the m\u00e9nage \u00e0 trois of cancer: implications for immunotherapy. Physiol Rev. 2020;100(1):1\u2013102.","journal-title":"Physiol Rev"},{"issue":"6","key":"1112_CR22","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1038\/nrc3064","volume":"11","author":"W Wilson","year":"2011","unstructured":"Wilson W, Hay M. Targeting hypoxia in cancer therapy. Nat Rev Cancer. 2011;11(6):393\u2013410.","journal-title":"Nat Rev Cancer"},{"issue":"3","key":"1112_CR23","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/j.jhep.2021.05.032","volume":"75","author":"L Ma","year":"2021","unstructured":"Ma L, Craig A, Heinrich S. Hypoxia is a key regulator in liver cancer progression. J Hepatol. 2021;75(3):736\u20137.","journal-title":"J Hepatol"},{"issue":"7","key":"1112_CR24","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1038\/s41556-018-0118-z","volume":"20","author":"J Garcia-Bermudez","year":"2018","unstructured":"Garcia-Bermudez J, Baudrier L, La K, Zhu X, Fidelin J, Sviderskiy V, et al. Aspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours. Nat Cell Biol. 2018;20(7):775\u201381.","journal-title":"Nat Cell Biol"},{"issue":"1","key":"1112_CR25","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s13045-019-0836-0","volume":"13","author":"L Yang","year":"2020","unstructured":"Yang L, Luo Q, Lu L, Zhu W, Sun H, Wei R, et al. Increased neutrophil extracellular traps promote metastasis potential of hepatocellular carcinoma via provoking tumorous inflammatory response. J Hematol Oncol. 2020;13(1):3.","journal-title":"J Hematol Oncol"},{"issue":"6","key":"1112_CR26","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1158\/0008-5472.CAN-15-1591","volume":"76","author":"S Tohme","year":"2016","unstructured":"Tohme S, Yazdani H, Al-Khafaji A, Chidi A, Loughran P, Mowen K, et al. Neutrophil extracellular traps promote the development and progression of liver metastases after surgical stress. Can Res. 2016;76(6):1367\u201380.","journal-title":"Can Res"},{"issue":"1","key":"1112_CR27","doi-asserted-by":"publisher","first-page":"218","DOI":"10.3324\/haematol.2019.217083","volume":"105","author":"Y Hisada","year":"2020","unstructured":"Hisada Y, Grover S, Maqsood A, Houston R, Ay C, Noubouossie D, et al. Neutrophils and neutrophil extracellular traps enhance venous thrombosis in mice bearing human pancreatic tumors. Haematologica. 2020;105(1):218\u201325.","journal-title":"Haematologica"},{"issue":"1","key":"1112_CR28","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.jhep.2015.02.009","volume":"63","author":"Y Liu","year":"2015","unstructured":"Liu Y, Yan W, Tohme S, Chen M, Fu Y, Tian D, et al. Hypoxia induced HMGB1 and mitochondrial DNA interactions mediate tumor growth in hepatocellular carcinoma through Toll-like receptor 9. J Hepatol. 2015;63(1):114\u201321.","journal-title":"J Hepatol"},{"issue":"1","key":"1112_CR29","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s13045-020-00920-3","volume":"13","author":"S Yuan","year":"2020","unstructured":"Yuan S, Liu Z, Xu Z, Liu J, Zhang J. High mobility group box 1 (HMGB1): a pivotal regulator of hematopoietic malignancies. J Hematol Oncol. 2020;13(1):91.","journal-title":"J Hematol Oncol"},{"issue":"5","key":"1112_CR30","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1172\/JCI31537","volume":"117","author":"W Lin","year":"2007","unstructured":"Lin W, Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Investig. 2007;117(5):1175\u201383.","journal-title":"J Clin Investig"},{"issue":"6245","key":"1112_CR31","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1126\/science.aaa8064","volume":"349","author":"A Warnatsch","year":"2015","unstructured":"Warnatsch A, Ioannou M, Wang Q, Papayannopoulos V. Inflammation. Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis. Science (New York, NY). 2015;349(6245):316\u201320.","journal-title":"Science (New York, NY)"},{"issue":"6409","key":"1112_CR32","doi-asserted-by":"publisher","first-page":"eaao4227","DOI":"10.1126\/science.aao4227","volume":"361","author":"J Albrengues","year":"2018","unstructured":"Albrengues J, Shields M, Ng D, Park C, Ambrico A, Poindexter M, et al. Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science (New York, NY). 2018;361(6409):eaao4227.","journal-title":"Science (New York, NY)"},{"issue":"1","key":"1112_CR33","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/s12943-019-1089-9","volume":"18","author":"X Jing","year":"2019","unstructured":"Jing X, Yang F, Shao C, Wei K, Xie M, Shen H, et al. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol Cancer. 2019;18(1):157.","journal-title":"Mol Cancer"},{"key":"1112_CR34","doi-asserted-by":"publisher","first-page":"702726","DOI":"10.3389\/fimmu.2021.702726","volume":"12","author":"EN Scott","year":"2021","unstructured":"Scott EN, Gocher AM, Workman CJ, Vignali DAA. Regulatory T Cells: Barriers of Immune Infiltration Into the Tumor Microenvironment. Front Immunol. 2021;12:702726.","journal-title":"Front Immunol"},{"key":"1112_CR35","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.jconrel.2020.05.029","volume":"324","author":"C Phung","year":"2020","unstructured":"Phung C, Tran T, Pham L, Nguyen H, Jeong J, Yong C, et al. Current developments in nanotechnology for improved cancer treatment, focusing on tumor hypoxia. J Controlled Release\u202f: Official J Controlled Release Soc. 2020;324:413\u201329.","journal-title":"J Controlled Release : Official J Controlled Release Soc"},{"key":"1112_CR36","doi-asserted-by":"publisher","first-page":"27","DOI":"10.3389\/fcell.2016.00027","volume":"4","author":"P McDonald","year":"2016","unstructured":"McDonald P, Chafe S, Dedhar S. Overcoming hypoxia-mediated tumor progression: combinatorial approaches targeting ph regulation, angiogenesis and immune dysfunction. Front Cell Develop Biol. 2016;4:27.","journal-title":"Front Cell Develop Biol"},{"key":"1112_CR37","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.3389\/fimmu.2017.01887","volume":"8","author":"P Vaupel","year":"2017","unstructured":"Vaupel P, Multhoff G. Accomplices of the hypoxic tumor microenvironment compromising antitumor immunity: adenosine, lactate, acidosis, vascular endothelial growth factor, potassium ions, and phosphatidylserine. Front Immunol. 2017;8:1887.","journal-title":"Front Immunol"},{"issue":"8","key":"1112_CR38","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/j.tips.2017.05.002","volume":"38","author":"G Qiu","year":"2017","unstructured":"Qiu G, Jin M, Dai J, Sun W, Feng J, Jin W. Reprogramming of the tumor in the hypoxic niche: the emerging concept and associated therapeutic strategies. Trends Pharmacol Sci. 2017;38(8):669\u201386.","journal-title":"Trends Pharmacol Sci"},{"issue":"15","key":"1112_CR39","doi-asserted-by":"publisher","first-page":"3741","DOI":"10.1158\/1078-0432.CCR-17-1703","volume":"24","author":"Y Jin","year":"2018","unstructured":"Jin Y, Zhang P, Wang Y, Jin B, Zhou J, Zhang J, et al. Neddylation blockade diminishes hepatic metastasis by dampening cancer stem-like cells and angiogenesis in uveal melanoma. Clin Cancer Res. 2018;24(15):3741\u201354.","journal-title":"Clin Cancer Res"},{"key":"1112_CR40","doi-asserted-by":"publisher","first-page":"2155","DOI":"10.3389\/fimmu.2019.02155","volume":"10","author":"P Lecot","year":"2019","unstructured":"Lecot P, Sarabi M, Pereira Abrantes M, Mussard J, Koenderman L, Caux C, et al. Neutrophil heterogeneity in cancer: from biology to therapies. Front Immunol. 2019;10:2155.","journal-title":"Front Immunol"},{"issue":"32","key":"1112_CR41","doi-asserted-by":"publisher","first-page":"13076","DOI":"10.1073\/pnas.1200419109","volume":"109","author":"M Demers","year":"2012","unstructured":"Demers M, Krause D, Schatzberg D, Martinod K, Voorhees J, Fuchs T, et al. Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis. Proc Natl Acad Sci USA. 2012;109(32):13076\u201381.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"1112_CR42","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1111\/j.1538-7836.2011.04544.x","volume":"10","author":"A Brill","year":"2012","unstructured":"Brill A, Fuchs T, Savchenko A, Thomas G, Martinod K, De Meyer S, et al. Neutrophil extracellular traps promote deep vein thrombosis in mice. J Thrombosis Haemostasis\u202f: JTH. 2012;10(1):136\u201344.","journal-title":"J Thrombosis Haemostasis : JTH"},{"issue":"8","key":"1112_CR43","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1038\/nm.2184","volume":"16","author":"S Massberg","year":"2010","unstructured":"Massberg S, Grahl L, von Bruehl M, Manukyan D, Pfeiler S, Goosmann C, et al. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med. 2010;16(8):887\u201396.","journal-title":"Nat Med"},{"issue":"361","key":"1112_CR44","doi-asserted-by":"publisher","first-page":"361ra138","DOI":"10.1126\/scitranslmed.aag1711","volume":"8","author":"J Park","year":"2016","unstructured":"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.","journal-title":"Sci Transl Med"},{"issue":"7814","key":"1112_CR45","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/s41586-020-2394-6","volume":"583","author":"L Yang","year":"2020","unstructured":"Yang L, Liu Q, Zhang X, Liu X, Zhou B, Chen J, et al. DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25. Nature. 2020;583(7814):133\u20138.","journal-title":"Nature"},{"issue":"5","key":"1112_CR46","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.3892\/or.2014.3413","volume":"32","author":"Z Cheng","year":"2014","unstructured":"Cheng Z, Cui W, Ding Y, Liu T, Liu W, Qin Y, et al. BMP8B mediates the survival of pancreatic cancer cells and regulates the progression of pancreatic cancer. Oncol Rep. 2014;32(5):1861\u20136.","journal-title":"Oncol Rep"},{"issue":"1","key":"1112_CR47","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1186\/s12943-018-0898-6","volume":"17","author":"X Zhang","year":"2018","unstructured":"Zhang X, Shi H, Yuan X, Jiang P, Qian H, Xu W. Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration. Mol Cancer. 2018;17(1):146.","journal-title":"Mol Cancer"},{"issue":"6","key":"1112_CR48","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1158\/1078-0432.CCR-18-1226","volume":"25","author":"M Nie","year":"2019","unstructured":"Nie M, Yang L, Bi X, Wang Y, Sun P, Yang H, et al. Neutrophil extracellular traps induced by IL8 promote diffuse large B-cell lymphoma progression via the TLR9 signaling. Clin Cancer Res. 2019;25(6):1867\u201379.","journal-title":"Clin Cancer Res"}],"container-title":["Cell Communication and Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-023-01112-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12964-023-01112-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-023-01112-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T14:28:24Z","timestamp":1683556104000},"score":1,"resource":{"primary":{"URL":"https:\/\/biosignaling.biomedcentral.com\/articles\/10.1186\/s12964-023-01112-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,1]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["1112"],"URL":"https:\/\/doi.org\/10.1186\/s12964-023-01112-5","relation":{"has-part":[{"id-type":"doi","id":"https:\/\/doi.org\/10.21203\/rs.3.rs-2908668\/v1","asserted-by":"subject"}]},"ISSN":["1478-811X"],"issn-type":[{"value":"1478-811X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,1]]},"assertion":[{"value":"3 December 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"We extracted blood and tissue samples from GC patients who consented to this study in writing. Protocol for this study including clinical patients and animals were approved by the ethics committee of the First Affiliated Hospital of Jiamusi University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"86"}}