{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T20:47:06Z","timestamp":1761598026831},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,1,12]],"date-time":"2019-01-12T00:00:00Z","timestamp":1547251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81702677"],"award-info":[{"award-number":["81702677"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2016HM39","ZR2016HM02"],"award-info":[{"award-number":["ZR2016HM39","ZR2016HM02"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:p>Carcinoembryonic antigen cell adhesion molecule 1 (<jats:styled-content style=\"fixed-case\">CEACAM<\/jats:styled-content>1), a transmembrane glycoprotein, has multiple functions. In tongue squamous cell carcinoma (<jats:styled-content style=\"fixed-case\">TSCC<\/jats:styled-content>), <jats:styled-content style=\"fixed-case\">CEACAM<\/jats:styled-content>1 overexpression is correlated with neutrophil infiltration, and both are associated with poor clinical outcomes. However, the mechanism underlying <jats:styled-content style=\"fixed-case\">CEACAM<\/jats:styled-content>1's effect on neutrophil function in <jats:styled-content style=\"fixed-case\">TSCC<\/jats:styled-content> remains unclear. We cocultured tongue carcinoma cells overexpressing <jats:styled-content style=\"fixed-case\">CEACAM<\/jats:styled-content>1\u20104L, <jats:styled-content style=\"fixed-case\">CEACAM<\/jats:styled-content>1\u20104S and differentiated <jats:styled-content style=\"fixed-case\">HL<\/jats:styled-content>\u201060 cells. This significantly upregulated the expression of <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u20109, interleukin 8, and <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\u2010A in the differentiated <jats:styled-content style=\"fixed-case\">HL<\/jats:styled-content>\u201060 cells and downregulated the expression of <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1, relative to vector and blank control groups (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.05). Additionally, <jats:styled-content style=\"fixed-case\">CEACAM<\/jats:styled-content>1 overexpression in tongue carcinoma cells weakened the cytotoxicity of differentiated <jats:styled-content style=\"fixed-case\">HL<\/jats:styled-content>\u201060 cells in the coculture system (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.05). Thus, <jats:styled-content style=\"fixed-case\">CEACAM<\/jats:styled-content>1 expression in <jats:styled-content style=\"fixed-case\">TSCC<\/jats:styled-content> may induce an antitumor to protumor transformation of neutrophils. We performed <jats:styled-content style=\"fixed-case\">qRT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content> to evaluate the underlying mechanism, and found that <jats:styled-content style=\"fixed-case\">CEACAM<\/jats:styled-content>1 expression in tongue carcinoma cells upregulated transforming growth factor \u03b21 (<jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b21) expression, while blocking of <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b21 inhibited the neutrophils\u2019 changes in the coculture system. Immunohistochemical analysis of clinical specimens revealed strong expression of <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b21 protein in <jats:styled-content style=\"fixed-case\">TSCC<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b21 expression was positively correlated with <jats:styled-content style=\"fixed-case\">CEACAM<\/jats:styled-content>1 expression, lymph node metastasis, and tumor recurrence. Double immunofluorescence results revealed colocalization of <jats:styled-content style=\"fixed-case\">CEACAM<\/jats:styled-content>1 and <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b21 protein in <jats:styled-content style=\"fixed-case\">TSCC<\/jats:styled-content>. A xenograft nude mouse model revealed that <jats:styled-content style=\"fixed-case\">CEACAM<\/jats:styled-content>1 overexpression in <jats:styled-content style=\"fixed-case\">TSCC<\/jats:styled-content> promoted tumor formation and growth, and was associated with more neutrophils infiltration. Our results indicate that <jats:styled-content style=\"fixed-case\">CEACAM<\/jats:styled-content>1 overexpression in <jats:styled-content style=\"fixed-case\">TSCC<\/jats:styled-content> may induce transformation of neutrophils from antitumor to protumor type via <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b21, which may further promote tumor progression.<\/jats:p>","DOI":"10.1111\/cas.13909","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T12:13:55Z","timestamp":1545221635000},"page":"519-529","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Carcinoembryonic antigen cell adhesion molecule 1 inhibits the antitumor effect of neutrophils in tongue squamous cell carcinoma"],"prefix":"10.1111","volume":"110","author":[{"given":"Ning","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathology School of Basic Medicine Medical College of Qingdao University  Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences Qilu Hospital Shandong University  Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinghua","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Pathology School of Basic Medicine Medical College of Qingdao University  Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenggang","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Pathology School of Basic Medicine Medical College of Qingdao University  Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathology School of Basic Medicine Medical College of Qingdao University  Qingdao 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