{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:39:48Z","timestamp":1790779188145,"version":"4.1.0"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Natural Science Funds Fund"},{"name":"Anhui Institute of Translational Medicine","award":["2017zhyx36"],"award-info":[{"award-number":["2017zhyx36"]}]},{"name":"Anhui Institute of Translational Medicine","award":["2017zhyx36"],"award-info":[{"award-number":["2017zhyx36"]}]},{"name":"Special Fund for Discipline Leaders of Anhui Province","award":["2019H230"],"award-info":[{"award-number":["2019H230"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,29]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The immune component of the tumor microenvironment is essential for the regulation of cancer progression. In breast cancer (BC), a patient's tumor mass is frequently infiltrated by neutrophils (tumor-associated neutrophils, TANs). Our study addressed the role of TANs and their mechanism of action in BC. Using quantitative IHC, ROC, and Cox analysis, we demonstrated that a high density of TANs infiltrating the tumor parenchyma was predictive of poor prognosis and of decreased progression-free survival of patients with BC, who underwent surgical tumor removal without previous neoadjuvant chemotherapy, in 3 different cohorts: training, validation, and independent cohorts. Conditioned medium from human BC cell lines prolonged the lifespan of healthy donor neutrophils ex vivo. Neutrophils activated by the supernatants of BC lines demonstrated an increased ability to stimulate proliferation, migration, and invasive activity of BC cells. Cytokines involved in this process were identified using antibody arrays. The relationship between these cytokines and the density of TANs was validated by ELISA and IHC in fresh BC surgical samples. It was determined that tumor-derived G-CSF significantly extended the lifespan and increased the metastasis-promoting activities of neutrophils via the PI3K-AKT and NF-\u03baB pathways. Simultaneously, TAN-derived RLN2 promoted the migratory abilities of MCF7 cells via PI3K-AKT-MMP-9. Analysis of tumor tissues from 20 patients with BC identified a positive correlation between the density of TANs and the activation of the G-CSF-RLN2-MMP-9 axis. Finally, our data demonstrated that TANs in human BC have detrimental effects, supporting malignant cell invasion and migration.<\/jats:p>","DOI":"10.1093\/jleuko\/qiad004","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T11:17:18Z","timestamp":1674040638000},"page":"383-399","source":"Crossref","is-referenced-by-count":53,"title":["Tumor-activated neutrophils promote metastasis in breast cancer via the G-CSF-RLN2-MMP-9 axis"],"prefix":"10.1093","volume":"113","author":[{"given":"Youjing","family":"Sheng","sequence":"first","affiliation":[{"name":"Department of Pathology, The First Affiliated Hospital of Anhui Medical University , 218 Jixi Road, Shushan District, Hefei 230022, Anhui , PR China"},{"name":"Institute of Transfusion Medicine and Immunology, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, University of Heidelberg , Ludolf-Krehl Strasse 13-17, 68167 Mannheim , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First Affiliated Hospital of Anhui Medical University , 218 Jixi Road, Shushan District, Hefei 230022, Anhui , PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Anhui Medical University , Hefei, Anhui 230032 , PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanqing","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Second Affiliated Hospital of Anhui Medical University , 678 Furong Road, Shushan District, Hefei, Anhui 230601 , PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Affiliated Hospital of Anhui Medical University , 678 Furong Road, Shushan District, Hefei, Anhui 230601 , PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis Boafo","family":"Kwantwi","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First Affiliated Hospital of Anhui Medical University , 218 Jixi Road, Shushan District, Hefei 230022, Anhui , PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiezhen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Anhui Medical University , 81 Meishan Road, Shushan District, Hefei, Anhui 230032 , PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiegou","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Immunology, Anhui Medical University , 81 Meishan Road, Hefei, Anhui 230032 , PR 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University , Moskovskiy Trakt, 2, 634050 Tomsk, Tomsk Oblast , Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First Affiliated Hospital of Anhui Medical University , 218 Jixi Road, Shushan District, Hefei 230022, Anhui , PR China"},{"name":"Department of Pathology, Anhui Medical University , 81 Meishan Road, Shushan District, Hefei, Anhui 230032 , PR China"},{"name":"Laboratory of Translational Cellular and Molecular Biomedicine, Tomsk State University , Lenin Ave, 36, 634050 Tomsk, Tomsk Oblast , Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"issue":"2","key":"2023032923111060900_","doi-asserted-by":"crossref","first-page":"115","DOI":"10.3322\/caac.21338","article-title":"Cancer statistics in China, 2015","volume":"66","author":"Chen","year":"2016","journal-title":"CA 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