{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:26:47Z","timestamp":1793305607642,"version":"4.5.0"},"reference-count":65,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":48,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Terry Fox Research Institute Program Group Grant","award":["251691"],"award-info":[{"award-number":["251691"]}]},{"name":"Canadian Cancer Society Impact Grant","award":["263780"],"award-info":[{"award-number":["263780"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institute of Health Research","doi-asserted-by":"crossref","award":["Foundation grant 148373,bridge grant PLL-185690,Project grant PJT-190027,CGV 192738,PJT-203842"],"award-info":[{"award-number":["Foundation grant 148373,bridge grant PLL-185690,Project grant PJT-190027,CGV 192738,PJT-203842"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009326","name":"Cancer Research Society","doi-asserted-by":"crossref","award":["1281449"],"award-info":[{"award-number":["1281449"]}],"id":[{"id":"10.13039\/100009326","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,23]]},"abstract":"<jats:p>Immunosuppression and metastasis are critical hallmarks of breast cancer, often linked to poor patient outcomes. The secreted cytokine chitinase-3\u2013like 1 (CHI3L1) is frequently overexpressed in breast cancer samples and promotes an immunosuppressed tumor microenvironment. Notably, CHI3L1 expression is elevated in metastatic patient samples when compared with the matched primary breast tumor. To investigate its role in breast cancer metastasis, we generated an inducible genetically engineered mouse model that overexpresses CHI3L1 in the mammary epithelium. Ectopic expression of CHI3L1 in the polyomavirus middle T (PyMT) mouse model of breast cancer suppressed antitumor immune responses, accelerated mammary tumor onset, and enhanced lung metastasis. Mechanistically, elevated CHI3L1 expression in the mammary epithelium enhanced neutrophil recruitment, which subsequently degraded the extracellular matrix and increased the number of circulating tumor cells. These findings reveal a key mechanism driving metastatic dissemination and argue that therapeutically targeting Chi3l1 could enhance antitumor immunity and suppress metastasis.<\/jats:p>","DOI":"10.1172\/jci.insight.199307","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T17:00:18Z","timestamp":1770138018000},"source":"Crossref","is-referenced-by-count":3,"title":["The CHI3L1-neutrophil axis drives immune suppression and breast cancer metastatic dissemination"],"prefix":"10.1172","volume":"11","author":[{"given":"Tarek","family":"Taifour","sequence":"first","affiliation":[{"name":"McGill University, Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, Montreal, Quebec, Canada."},{"name":"Rosalind and Morris Goodman Cancer Institute, Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad\u00e9line","family":"Mass\u00e9","sequence":"additional","affiliation":[{"name":"Rosalind and Morris Goodman Cancer Institute, Montreal, Quebec, Canada."},{"name":"McGill University, Department of Biochemistry, Faculty of Medicine, Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Gu","sequence":"additional","affiliation":[{"name":"Rosalind and Morris Goodman Cancer Institute, Montreal, Quebec, Canada."},{"name":"McGill University, Department of Biochemistry, Faculty of Medicine, Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Sanguin-Gendreau","sequence":"additional","affiliation":[{"name":"Rosalind and Morris Goodman Cancer Institute, Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Zuo","sequence":"additional","affiliation":[{"name":"Rosalind and Morris Goodman Cancer Institute, Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Xiao","sequence":"additional","affiliation":[{"name":"Rosalind and Morris Goodman Cancer Institute, Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Solymoss","sequence":"additional","affiliation":[{"name":"McGill University, Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, Montreal, Quebec, Canada."},{"name":"Rosalind and Morris Goodman Cancer Institute, Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyun","family":"Shen","sequence":"additional","affiliation":[{"name":"Rosalind and Morris Goodman Cancer Institute, Montreal, Quebec, Canada."},{"name":"McGill University, Department of Biochemistry, Faculty of Medicine, Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailey","family":"Proud","sequence":"additional","affiliation":[{"name":"Rosalind and Morris Goodman Cancer Institute, Montreal, Quebec, Canada."},{"name":"McGill University, Department of Biochemistry, Faculty of Medicine, Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4193-6393","authenticated-orcid":true,"given":"Sherif Samer","family":"Attalla","sequence":"additional","affiliation":[{"name":"Rosalind and Morris Goodman Cancer Institute, Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasilios","family":"Papavasiliou","sequence":"additional","affiliation":[{"name":"Rosalind and Morris Goodman Cancer Institute, Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy U.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa E.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalie","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9514-3658","authenticated-orcid":true,"given":"Chun Geun","family":"Lee","sequence":"additional","affiliation":[{"name":"Brown University, Molecular Biology and Immunology, Providence, Rhode Island, USA."},{"name":"Hanyang University, Intercollege, Seoul, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9847-1211","authenticated-orcid":true,"given":"Suchitra","family":"Kamle","sequence":"additional","affiliation":[{"name":"Brown University, Molecular Biology and Immunology, Providence, Rhode Island, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josie","family":"Ursini-Siegel","sequence":"additional","affiliation":[{"name":"McGill University, Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, Montreal, Quebec, Canada."},{"name":"McGill University, Department of Biochemistry, Faculty of Medicine, Montreal, Quebec, Canada."},{"name":"Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3124-8557","authenticated-orcid":true,"given":"Jack A.","family":"Elias","sequence":"additional","affiliation":[{"name":"Brown University, Molecular Biology and Immunology, Providence, Rhode Island, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Siegel","sequence":"additional","affiliation":[{"name":"McGill University, Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, Montreal, Quebec, Canada."},{"name":"Rosalind and Morris Goodman Cancer Institute, Montreal, Quebec, Canada."},{"name":"McGill University, Department of Biochemistry, Faculty of Medicine, Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinath","family":"Jeselsohn","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Muller","sequence":"additional","affiliation":[{"name":"McGill University, Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, Montreal, Quebec, Canada."},{"name":"Rosalind and Morris Goodman Cancer Institute, Montreal, Quebec, Canada."},{"name":"McGill University, Department of Biochemistry, Faculty of Medicine, Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"issue":"5","key":"B1","first-page":"311","article-title":"Breast cancer metastasis","volume":"9","author":"Scully","year":"2012","journal-title":"Cancer Genomics Proteomics"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2015.08.009"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-01161-4"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-024-00638-2"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-70788-3"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-015-1376-x"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1111796"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-019-1206-z"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29923"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1186\/bcr3603"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-01560-0"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-2770"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.257451"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061984"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/path.3961"},{"issue":"12","key":"B16","first-page":"4423","article-title":"High levels of serum HER-2\/neu and YKL-40 independently reflect aggressiveness of metastatic breast cancer","volume":"9","author":"Jensen","year":"2003","journal-title":"Clin Cancer Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.65"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081271"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1056397"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-018-0876-2"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.11.002"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/cancers6020897"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2020.12.6.1012"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.498"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.breast.2013.07.012"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00122.2022"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-020-09951-1"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-024-01244-9"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.741884"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1735"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2021.10.006"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1172\/JCI137750"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-53023-9"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu191"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqac055"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.33696\/Signaling.2.050"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.13138"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21754"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-017-0408-0"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3233\/CBM-160255"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26379"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-021-01187-y"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67484"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118699"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.05.031"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.31557\/APJCP.2025.26.1.207"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-021-07789-6"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao4227"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/1815098"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/nature16140"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-20301-6_4"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27841"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0551com"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.6.2846"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.03.008"},{"key":"B57","doi-asserted-by":"crossref","unstructured":"Ruhland S, et al. Inhibition of neutrophil degranulation by Nexinhib20 delays the development of radiation-induced pulmonary fibrosis [preprint]. https:\/\/doi.org\/10.1101\/2025.10.22.684057 Posted on bioRxiv Octover 23, 2025","DOI":"10.1101\/2025.10.22.684057"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.07.014"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107571"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-22-0140"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14638"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-02107-7"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1003034107"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.05.091"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-3052-5_22"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/199307\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:27:58Z","timestamp":1778873278000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/199307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,3]]},"references-count":65,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3,23]]},"published-print":{"date-parts":[[2026,3,23]]}},"alternative-id":["10.1172\/jci.insight.199307"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.199307","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,3]]},"article-number":"e199307"}}