{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:28:40Z","timestamp":1780316920534,"version":"3.54.1"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T00:00:00Z","timestamp":1666828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JSPS KAKENHI 21K07945"],"award-info":[{"award-number":["JSPS KAKENHI 21K07945"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JSPS KAKENHI 21K07985"],"award-info":[{"award-number":["JSPS KAKENHI 21K07985"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JSPS KAKENHI 21K16846"],"award-info":[{"award-number":["JSPS KAKENHI 21K16846"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The CXCL12\/CXCR4 axis plays a pivotal role in the progression of various malignancies, including oral squamous cell carcinoma (OSCC). In this study, we aimed to clarify the biological and clinical significance of CXCL12 in the tumor microenvironment of OSCCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Publicly available single\u2010cell RNA\u2010sequencing (RNA\u2010seq) datasets were used to analyze CXCL12 expression in head and neck squamous cell carcinomas (HNSCC). Immunohistochemical analysis of CXCL12, \u03b1\u2010smooth muscle antigen (\u03b1\u2010SMA), fibroblast activation protein (FAP) and CD8 was performed in a series of 47 surgically resected primary tongue OSCCs. Human skeletal muscle cells were co\u2010cultured with or without OSCC cells, after which CXCL12 expression was analyzed using quantitative reverse\u2010transcription PCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Analysis of the RNA\u2010seq data suggested CXCL12 is abundantly expressed in stromal cells within HNSCC tissue. Immunohistochemical analysis showed that in grade 1 primary OSCCs, CXCL12 is expressed in both tumor cells and muscle cells. By contrast, grade 3 tumors were characterized by disruption of muscle structure and reduced CXCL12 expression. Quantitative analysis of CXCL12\u2010positive areas within tumors revealed that reduced CXCL12 expression correlated with poorer overall survival. Levels of CXCL12 expression tended to inversely correlate \u03b1\u2010SMA expression and positively correlate with infiltration by CD8+ lymphocytes, though these relations did not reach statistical significance. CXCL12 was significantly upregulated in muscle cells co\u2010cultured with OSCC cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that tongue OSCC cells activate CXCL12 expression in muscle cells, which may contribute to tumor progression. However, CXCL12 is reduced in advanced OSCCs due to muscle tissue destruction.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5392","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T11:49:43Z","timestamp":1666871383000},"page":"5953-5963","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["CXCL12 is expressed by skeletal muscle cells in tongue oral squamous cell carcinoma"],"prefix":"10.1002","volume":"12","author":[{"given":"Akira","family":"Yorozu","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Sapporo Medical University School of Medicine  Sapporo Japan"},{"name":"Department of Molecular Biology Sapporo Medical University School of Medicine  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Sekiguchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology 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