{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:05:10Z","timestamp":1789661110418,"version":"4.0.1"},"reference-count":42,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2014,10,23]],"date-time":"2014-10-23T00:00:00Z","timestamp":1414022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Finnish Cancer Society"},{"name":"Sigrid Juselius Foundation"},{"name":"Cancer Foundation of Northern Ostrobotnia"},{"DOI":"10.13039\/501100007083","name":"Orion-Farmos Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007083","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004756","name":"Emil Aaltonen Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004756","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Vatsatautien tutkimuss\u00e4\u00e4ti\u00f6"},{"DOI":"10.13039\/100015738","name":"Mary and Georg C. Ehrnrooth Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008723","name":"Finnish Medical Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008723","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003125","name":"Finnish Cultural Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003125","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Toll\u2010like receptor 9 (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9) is a cellular receptor, which recognizes bacterial and host\u2010derived <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>. Stimulation of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 induces cellular invasion via matrix metalloproteinase 13 (<jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u201013). The aim of this study was to evaluate the role of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 in invasion of oral tongue squamous cell carcinoma (<jats:styled-content style=\"fixed-case\">OTSCC<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The effects of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 ligands on oral squamous cell carcinoma cell lines were studied with invasion and migration assays, as well as in a myoma organotypic model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 ligand, CpG\u2010<jats:styled-content style=\"fixed-case\">ODN<\/jats:styled-content>, increased invasion and migration in <jats:styled-content style=\"fixed-case\">OTSCC<\/jats:styled-content> lines. These effects were reduced by <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> or inhibition with <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 antibodies. Immunohistochemical analysis of tissues from 195 patients with <jats:styled-content style=\"fixed-case\">OTSCC<\/jats:styled-content> revealed that <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 was expressed in 181\/195 carcinomas. The expression of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 was higher in the malignant cells than in the normal epithelium. High <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 expression was associated with high <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u201013 expression and poor differentiation. High <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 expression was also identified as an independent predictor of poor prognosis (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content> 1.810, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> [1.053\u20133.112]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Toll\u2010like receptor 9 mediates <jats:styled-content style=\"fixed-case\">OTSCC<\/jats:styled-content> invasion and migration <jats:italic>in vitro<\/jats:italic> and is an independent prognostic factor of <jats:styled-content style=\"fixed-case\">OTSCC<\/jats:styled-content>. Inhibition of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 may be a novel therapeutic opportunity in oral cancer.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.12272","type":"journal-article","created":{"date-parts":[[2014,10,23]],"date-time":"2014-10-23T10:44:04Z","timestamp":1414061044000},"page":"571-577","source":"Crossref","is-referenced-by-count":23,"title":["Toll\u2010like receptor 9 mediates invasion and predicts prognosis in squamous cell carcinoma of the mobile tongue"],"prefix":"10.1111","volume":"44","author":[{"given":"Joonas H.","family":"Kauppila","sequence":"first","affiliation":[{"name":"Department of Pathology University of Oulu Oulu Finland"},{"name":"Department of Surgery University of Oulu Oulu Finland"},{"name":"Medical Research Center Oulu Oulu Finland"},{"name":"Oulu University Hospital Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Korvala","sequence":"additional","affiliation":[{"name":"Medical Research Center Oulu Oulu Finland"},{"name":"Department of Dentistry University of Oulu Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristiina","family":"Siiril\u00e4","sequence":"additional","affiliation":[{"name":"Department of Dentistry University of Oulu Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Manni","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Oulu Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura K.","family":"M\u00e4kinen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Head and Neck Surgery University of Helsinki Helsinki Finland"},{"name":"Department of Otorhinolaryngology and Head and Neck Surgery Helsinki University Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaana","family":"Hagstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Pathology Haartman Institute University of Helsinki Helsinki Finland"},{"name":"Huslab Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Atula","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Head and Neck Surgery University of Helsinki Helsinki Finland"},{"name":"Department of Otorhinolaryngology and Head and Neck Surgery Helsinki University Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caj","family":"Haglund","sequence":"additional","affiliation":[{"name":"Research Programs Unit Translational Cancer Biology University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katri S.","family":"Selander","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Alabama at Birmingham Birmingham AL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"Saarnio","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Oulu Oulu Finland"},{"name":"Medical Research Center Oulu Oulu Finland"},{"name":"Oulu University Hospital Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuomo J.","family":"Karttunen","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Oulu Oulu Finland"},{"name":"Medical Research Center Oulu Oulu Finland"},{"name":"Oulu University Hospital Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petri P.","family":"Lehenkari","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Oulu Oulu Finland"},{"name":"Medical Research Center Oulu Oulu Finland"},{"name":"Oulu University Hospital Oulu Finland"},{"name":"Anatomy and Cell biology University of Oulu Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuula","family":"Salo","sequence":"additional","affiliation":[{"name":"Medical Research Center Oulu Oulu Finland"},{"name":"Oulu University Hospital Oulu Finland"},{"name":"Department of Dentistry University of Oulu Oulu Finland"},{"name":"Department of Pathology Haartman Institute University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,10,23]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2009.09.006"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141126"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2006.02.023"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1358.027"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-6-1"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-07-2005"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20562"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000151602"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2011.03991.x"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-009-9162-0"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2005.02.009"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000329115"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.12.8242"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-06-0007"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.6.11.4826"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/apm.12016"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.20573"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.1989.tb00767.x"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/00016480510012273"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2010.10.013"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.21567"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.21856"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2012.589"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2012.01169.x"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2011.01.010"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092748"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-012-2181-7"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.081110"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2011.01110.x"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.2009.954354"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/35047123"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-008-9536-2"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12160"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.3402\/jom.v2i0.5195"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-3-27"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/609579"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006520"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.4161\/onci.23620"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crvi.2004.04.002"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06116"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-013-2762-0"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070925"}],"container-title":["Journal of Oral Pathology &amp; Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjop.12272","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjop.12272","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jop.12272","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T05:49:58Z","timestamp":1696225798000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jop.12272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,23]]},"references-count":42,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2015,9]]}},"alternative-id":["10.1111\/jop.12272"],"URL":"https:\/\/doi.org\/10.1111\/jop.12272","archive":["Portico"],"relation":{},"ISSN":["0904-2512","1600-0714"],"issn-type":[{"value":"0904-2512","type":"print"},{"value":"1600-0714","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,23]]}}}