{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T14:02:49Z","timestamp":1776780169677,"version":"3.51.2"},"reference-count":44,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2015,3,13]],"date-time":"2015-03-13T00:00:00Z","timestamp":1426204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Nippon Dental University at Tokyo","award":["#2"],"award-info":[{"award-number":["#2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Oral squamous cell carcinoma exhibits a poor prognosis, caused by aggressive progression and early\u2010stage metastasis to cervical lymph nodes. Here, we developed a xenograft mouse model to explore the heterogeneity of the tumor microenvironment that may govern local invasion and nodal metastasis of tumor cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We transplanted five oral carcinoma cell lines into the tongues of nude mice and determined tongue tumor growth and micrometastatic dissemination by serially sectioning the tongue and lymph node lesions in combination with immunohistochemistry and computer\u2010assisted image analysis. Our morphometric analysis enabled a quantitative assessment of blood and lymphatic endothelial densities in the intratumoral and host stromal regions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All cell lines tested were tumorigenic in mouse tongue. The metastatic lesion\u2010derived carcinoma cell lines (<jats:styled-content style=\"fixed-case\">OSC<\/jats:styled-content>19, <jats:styled-content style=\"fixed-case\">OSC<\/jats:styled-content>20, and <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>2) yielded a 100% nodal metastasis rate, whereas the primary tumor\u2010derived cell lines (<jats:styled-content style=\"fixed-case\">KOSC<\/jats:styled-content>2 and <jats:styled-content style=\"fixed-case\">HO<\/jats:styled-content>\u20101\u2010u\u20101) showed &lt;40% metastatic potential. Immunohistochemistry showed that the individual cell lines gave rise to heterogeneous tumor architecture and phenotypes and that their micrometastatic lesions assimilated the immunophenotypic properties of the corresponding tongue tumors. Notably, <jats:styled-content style=\"fixed-case\">OSC<\/jats:styled-content>19 and <jats:styled-content style=\"fixed-case\">OSC<\/jats:styled-content>20 cells shared similar aggressive tumorigenicity in both the tongue and lymph node environments but displayed markedly diverse immunophenotypes and gene expression profiles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our model facilitated comparing the tumor microenvironments in tongue and lymph node lesions. The results support that tumorigenicity and tumor architecture in the host tongue environment depend on the origin and properties of the carcinoma cell lines and that metastatic progression may take place through heterogeneous tumor\u2013host interactions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.12318","type":"journal-article","created":{"date-parts":[[2015,3,13]],"date-time":"2015-03-13T06:23:42Z","timestamp":1426227822000},"page":"656-668","source":"Crossref","is-referenced-by-count":12,"title":["Heterogeneous tumor stromal microenvironments of oral squamous cell carcinoma cells in tongue and nodal metastatic lesions in a xenograft mouse model"],"prefix":"10.1111","volume":"44","author":[{"given":"Youichi","family":"Shirako","sequence":"first","affiliation":[{"name":"Department of Pathology School of Life Dentistry at Tokyo The Nippon Dental University Chiyoda\u2010ku, Tokyo 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Chiyoda\u2010ku, Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihito","family":"Shimazu","sequence":"additional","affiliation":[{"name":"Department of Pathology School of Life Dentistry at Tokyo The Nippon Dental University Chiyoda\u2010ku, Tokyo Japan"},{"name":"Department of Food and Life Sciences School of Life and Environmental Sciences Azabu University Chuo\u2010ku, Sagamihara Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaaki","family":"Aoba","sequence":"additional","affiliation":[{"name":"Department of Pathology School of Life Dentistry at Tokyo The Nippon Dental University Chiyoda\u2010ku, Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8466-6376","authenticated-orcid":false,"given":"Yuuichi","family":"Soeno","sequence":"additional","affiliation":[{"name":"Department of Pathology School of Life Dentistry at Tokyo The Nippon Dental University 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