{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T09:09:15Z","timestamp":1784365755799,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["305891\/2024\u20103"],"award-info":[{"award-number":["305891\/2024\u20103"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["Code 001"],"award-info":[{"award-number":["Code 001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Actinic cheilitis is a precursor to lip squamous cell carcinoma. How ultraviolet\u2010induced stromal degeneration relates to invasion\u2010related extracellular matrix markers remains unclear. This study investigated basophilic degeneration of collagen, solar elastosis, fibronectin, tenascin\u2010C, and podoplanin in both lesions.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Specimens of actinic cheilitis (\n n<\/jats:italic>\n \u2009=\u200928) and lip squamous cell carcinoma (\n n<\/jats:italic>\n \u2009=\u200928) were analyzed. Collagen degeneration, elastosis, and the immunoexpression of fibronectin, tenascin\u2010C, and podoplanin were quantified using digital image analysis. Associations were evaluated using mixed\u2010effects models.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Collagen degeneration and elastosis areas were significantly greater in actinic cheilitis (\n p<\/jats:italic>\n \u2009<\u20090.001). Lip squamous cell carcinoma exhibited higher stromal fibronectin and podoplanin (\n p<\/jats:italic>\n \u2009<\u20090.001), whereas epithelial tenascin\u2010C was higher in actinic cheilitis (\n p<\/jats:italic>\n \u2009<\u20090.001). Notably, in both lesions, areas with pronounced collagen degeneration and elastosis were inversely associated with the expression of these invasion\u2010related proteins.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Actinic cheilitis features marked actinic stromal degeneration, whereas lip squamous cell carcinoma exhibits tumor\u2010driven extracellular matrix remodeling with increased invasion\u2010related markers. These findings highlight distinct stromal microenvironment profiles associated with pre\u2010neoplastic and neoplastic lip lesions.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/odi.70427","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T08:46:27Z","timestamp":1784364387000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Matrix Remodeling in Actinic Cheilitis and Lip Squamous Cell Carcinoma: A Cross\u2010Sectional Study"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0043-527X","authenticated-orcid":false,"given":"Caroline","family":"Alfaia\u2010Silva","sequence":"first","affiliation":[{"name":"Graduate Program in Dentistry Federal University of Santa Catarina Florian\u00f3polis Santa Catarina Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7335-2026","authenticated-orcid":false,"given":"Polyane Caroline Arruda","family":"de Farias","sequence":"additional","affiliation":[{"name":"School of Dentistry Federal University of Santa Catarina Florian\u00f3polis Santa Catarina Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0172-9752","authenticated-orcid":false,"given":"Fernanda","family":"de Mello da Silva","sequence":"additional","affiliation":[{"name":"School of Dentistry Federal University of Santa Catarina Florian\u00f3polis Santa Catarina Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5234-3211","authenticated-orcid":false,"given":"Lidiane","family":"de Paula Ribeiro","sequence":"additional","affiliation":[{"name":"Graduate Program in Dentistry Federal University of Santa Catarina Florian\u00f3polis Santa Catarina Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5762-8315","authenticated-orcid":false,"given":"Ericles","family":"de Paiva Vieira","sequence":"additional","affiliation":[{"name":"Department of Physical Education State University of Santa Catarina Florian\u00f3polis Santa Catarina Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8516-8771","authenticated-orcid":false,"given":"Elena Riet Correa","family":"Rivero","sequence":"additional","affiliation":[{"name":"Department of Pathology Federal University of Santa Catarina Florian\u00f3polis Santa Catarina Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5395-0486","authenticated-orcid":false,"given":"Filipe","family":"Modolo","sequence":"additional","affiliation":[{"name":"Department of Pathology Federal University of Santa Catarina Florian\u00f3polis Santa Catarina Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.2174\/0929867330666230404124229","article-title":"Biology of Tenascin C and Its Role in Physiology and Pathology","volume":"31","author":"Abedsaeidi M.","year":"2024","journal-title":"CMC"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.4103\/0970-9290.79968","article-title":"Morphological and Ultrastructural Characteristics of Extracellular Matrix Changes in Oral Squamous Cell Carcinoma","volume":"22","author":"Agrawal U.","year":"2011","journal-title":"Indian Journal of Dental Research"},{"key":"e_1_2_12_4_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22083974","article-title":"Inflammatory Molecules Associated With Ultraviolet Radiation\u2010Mediated Skin Aging","volume":"22","author":"Ansary T. M.","year":"2021","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_12_5_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23031310","article-title":"The Role of Podoplanin in Skin Diseases","volume":"23","author":"Asai J.","year":"2022","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_12_6_1","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1007\/s00784-016-1956-3","article-title":"Podoplanin, Ezrin, and Rho\u2010A Proteins May Have Joint Participation in Tumor Invasion of Lip Cancer","volume":"21","author":"Assao A.","year":"2017","journal-title":"Clinical Oral Investigations"},{"key":"e_1_2_12_7_1","doi-asserted-by":"crossref","DOI":"10.3390\/cosmetics10020048","article-title":"Aging and the Impact of Solar Ultraviolet Radiation on the Expression of Type I and Type VI Collagen","volume":"10","author":"Biskanaki F.","year":"2023","journal-title":"Cosmetics"},{"key":"e_1_2_12_8_1","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1002\/hed.70018","article-title":"Podoplanin Expression and the Risk of Malignant Transformation of Oral Pre\u2010Malignant Disease: A Systematic Review and Meta\u2010Analysis","volume":"47","author":"Briggs E. 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K.","year":"2021","journal-title":"FEBS Journal"},{"key":"e_1_2_12_15_1","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1093\/bioinformatics\/btaa847","article-title":"Colour Deconvolution: Stain Unmixing in Histological Imaging (J Xu, Ed.)","volume":"37","author":"Landini G.","year":"2021","journal-title":"Bioinformatics"},{"key":"e_1_2_12_16_1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/jop.13541","article-title":"Assessment of the Association of Myofibroblasts and Structural Components of the Extracellular Matrix With Histopathological Parameters of Actinic Cheilitis and Lower Lip Squamous Cell Carcinoma","volume":"53","author":"Martinez F. E. 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D.","year":"2016","journal-title":"Advanced Drug Delivery Reviews"},{"key":"e_1_2_12_29_1","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2022.805425","article-title":"Actinic Cheilitis\u2014From Risk Factors to Therapy","volume":"9","author":"Vasilovici A.","year":"2022","journal-title":"Frontiers in Medicine"},{"key":"e_1_2_12_30_1","doi-asserted-by":"crossref","DOI":"10.1080\/14756366.2025.2488821","article-title":"Promoting Collagen Synthesis: A Viable Strategy to Combat Skin Ageing","volume":"40","author":"Wang S.","year":"2025","journal-title":"Journal of Enzyme Inhibition and Medicinal Chemistry"},{"key":"e_1_2_12_31_1","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2025.1554312","article-title":"The Role of Tenascin\u2010C in Tumor Microenvironments and Its Potential as a Therapeutic Target","volume":"13","author":"Wang Y.","year":"2025","journal-title":"Frontiers in Cell and Development Biology"},{"key":"e_1_2_12_32_1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1186\/s12935-020-01328-2","article-title":"Podoplanin Is Indispensable for Cell Motility and Platelet\u2010Induced Epithelial\u2010To\u2010Mesenchymal Transition\u2010Related Gene Expression in Esophagus Squamous Carcinoma TE11A Cells","volume":"20","author":"Watanabe N.","year":"2020","journal-title":"Cancer Cell International"},{"key":"e_1_2_12_33_1","doi-asserted-by":"crossref","first-page":"5120","DOI":"10.1038\/s41467-020-18794-x","article-title":"Concepts of Extracellular Matrix Remodelling in Tumour Progression and Metastasis","volume":"11","author":"Winkler J.","year":"2020","journal-title":"Nature Communications"},{"key":"e_1_2_12_34_1","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.actbio.2025.09.025","article-title":"Fibronectin Composition and Transglutaminase 2 Cross\u2010Linking Cooperatively Regulate Ovarian Cancer Cell Adhesion in ECM\u2010Mimetic Constructs","volume":"206","author":"Yang N.","year":"2025","journal-title":"Acta Biomaterialia"},{"key":"e_1_2_12_35_1","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.260244","article-title":"Advances on the Roles of Tenascin\u2010C in Cancer","volume":"135","author":"Yilmaz A.","year":"2022","journal-title":"Journal of Cell Science"}],"container-title":["Oral Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/odi.70427","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/odi.70427","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/odi.70427","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T08:46:32Z","timestamp":1784364392000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/odi.70427"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,18]]},"references-count":34,"alternative-id":["10.1111\/odi.70427"],"URL":"https:\/\/doi.org\/10.1111\/odi.70427","archive":["Portico"],"relation":{},"ISSN":["1354-523X","1601-0825"],"issn-type":[{"value":"1354-523X","type":"print"},{"value":"1601-0825","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,18]]},"assertion":[{"value":"2026-04-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"odi.70427"}}