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EMT was studied with syndecan\u20101, Cadherin\u201011, fibroblast\u2010specific protein (FSP)\u20101, <jats:bold><jats:italic>s<\/jats:italic><\/jats:bold>ecreted <jats:bold><jats:italic>p<\/jats:italic><\/jats:bold>rotein <jats:bold><jats:italic>a<\/jats:italic><\/jats:bold>cidic and <jats:bold><jats:italic>r<\/jats:italic><\/jats:bold>ich in <jats:bold><jats:italic>c<\/jats:italic><\/jats:bold>ysteine (SPARC) and Twist. Triple immunostaining in RLNs was used to highlight the carcinoma cells (E\u2010cadherin and Ki\u201067) and their relationship to the CAFs (\u03b1\u2010SMA). We found that metastatic RLNs hosted CAFs similarly as in pair\u2010matched primary tumors. Expression of EMT markers is common in both primary and metastatic tumors. We demonstrate that metastatic carcinoma cells (Ki\u201067 positive) downregulate E\u2010cadherin expression at the periphery of cancer islands, where they are in direct contact with CAFs. The supporting connective tissue microenvironment also commonly expresses syndecan\u20101, Cadherin\u201011, FSP\u20101, and SPARC. In conclusion, CAFs are common to both primary and metastatic SCC. We hypothesize that CAFs not only promote tumor invasion but also facilitate metastases, either by cometastasizing and\/or being recruited to lymph nodes. Evidence of EMT is common within primary tumors and metastatic SCC and may be further modulated by CAFs.<\/jats:p>","DOI":"10.1002\/ijc.25358","type":"journal-article","created":{"date-parts":[[2010,3,25]],"date-time":"2010-03-25T15:21:09Z","timestamp":1269530469000},"page":"1356-1362","source":"Crossref","is-referenced-by-count":103,"title":["Cancer\u2010associated fibroblasts and epithelial\u2010mesenchymal transition in metastatic oral tongue squamous cell carcinoma"],"prefix":"10.1002","volume":"127","author":[{"given":"Marilena","family":"Vered","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Dayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Yahalom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Dobriyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Barshack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim O.","family":"Bello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saara","family":"Kantola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuula","family":"Salo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,7,19]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1055-3207(18)30406-X"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01806129"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0046-8177(94)90122-8"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-007-9082-y"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2008.01471.x"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-09-0015"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2009.10.001"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2009.01.003"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2006.11.007"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12307-009-0020-0"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-2191"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2009.01357.x"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.036525"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1658"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36183"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-2017"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-009-0072-4"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090526"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.11.007"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2009.11.018"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-008-9135-x"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2009.01.015"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1636908"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2009.01419.x"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijom.2005.06.020"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.134.5.539"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2005.10.003"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604400"},{"key":"e_1_2_6_30_2","unstructured":"Invitrogen: Rabbit anti\u2010Cadherin 11 (OB\u2010Cadherin); Catalog No. 71\u20137600. 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