{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T19:20:06Z","timestamp":1784920806230,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tri-Service General Hospital","award":["TSGH- C107-037"],"award-info":[{"award-number":["TSGH- C107-037"]}]},{"name":"Tri-Service General Hospital","award":["TSGH-C108-056"],"award-info":[{"award-number":["TSGH-C108-056"]}]},{"name":"Tri-Service General Hospital","award":["TSGH-D-109-063"],"award-info":[{"award-number":["TSGH-D-109-063"]}]},{"name":"Tri-Service General Hospital","award":["TSGH-D-110-087"],"award-info":[{"award-number":["TSGH-D-110-087"]}]},{"name":"Tri-Service General Hospital","award":["TSGH-E-111206"],"award-info":[{"award-number":["TSGH-E-111206"]}]},{"name":"Tri-Service General Hospital","award":["MOST 107-2314-B-075B-005-MY3"],"award-info":[{"award-number":["MOST 107-2314-B-075B-005-MY3"]}]},{"name":"Ministry of Science Technology, China","award":["TSGH- C107-037"],"award-info":[{"award-number":["TSGH- C107-037"]}]},{"name":"Ministry of Science Technology, China","award":["TSGH-C108-056"],"award-info":[{"award-number":["TSGH-C108-056"]}]},{"name":"Ministry of Science Technology, China","award":["TSGH-D-109-063"],"award-info":[{"award-number":["TSGH-D-109-063"]}]},{"name":"Ministry of Science Technology, China","award":["TSGH-D-110-087"],"award-info":[{"award-number":["TSGH-D-110-087"]}]},{"name":"Ministry of Science Technology, China","award":["TSGH-E-111206"],"award-info":[{"award-number":["TSGH-E-111206"]}]},{"name":"Ministry of Science Technology, China","award":["MOST 107-2314-B-075B-005-MY3"],"award-info":[{"award-number":["MOST 107-2314-B-075B-005-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The tumor microenvironment (TME) plays a crucial role in tumor progression. One of its key stromal components, cancer-associated fibroblasts (CAFs), may crosstalk with cancer cells by secreting certain cytokines or chemokines. However, which important mediator(s) are released by CAFs, and the underlying molecular mechanism, remain largely unknown. In the present study, we isolated patient-derived CAFs and normal fibroblasts (NFs). Using microarray analysis, we detected chemokine ligand 11 (CCL11) overexpression in CAFs compared to NFs. CCL11 administration promoted the migration and invasion of head and neck cancer (HNC) cells with enhanced cancer stem cell-like properties and induction of epithelial-to-mesenchymal transition. Furthermore, neutralization of CCL11 activity reversed the aggressive phenotype of CAF-induced cancer cells. Confocal microscopy showed colocalization of CCL11 and CC chemokine receptor 3 (CCR3) on HNC cells. Moreover, immunohistochemical analysis of clinical samples from 104 patients with HNC showed that expression of CCL11 and CCR3 were significantly correlated with poor overall survival (p = 0.003 and 0.044, respectively). Collectively, CCL11 expressed on CAFs promotes HNC invasiveness, and neutralization of CCL11 reverses this effect. We propose that the CCL11\/CCR3 signaling circuit is a potential target for optimizing therapeutic strategies against HNC.<\/jats:p>","DOI":"10.3390\/cancers14133141","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T22:31:14Z","timestamp":1656369074000},"page":"3141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Cancer-Associated Fibroblasts Promote Tumor Aggressiveness in Head and Neck Cancer through Chemokine Ligand 11 and C-C Motif Chemokine Receptor 3 Signaling Circuit"],"prefix":"10.3390","volume":"14","author":[{"given":"Wen-Yen","family":"Huang","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"},{"name":"Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoh-Shiang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Nieh","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ming","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"},{"name":"Department of Pathology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsai-Yu","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Colon and Rectum Surgery, Department of Surgery, Tri-Service General Hospital Songshan Branch, National Defense Medical Center, Taipei 105, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Feng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dentistry, School of Dentistry, China Medical University, Taichung 406, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuender D.","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"},{"name":"Division of Medical Research, MacKay Children\u2019s Hospital, Taipei 104, Taiwan"},{"name":"Department of Immunology & Microbiology, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"686","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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