title: NANOG expression correlates with differentiation, metastasis and resistance to preoperative adjuvant therapy in oral squamous cell carcinoma.
abstract: NANOG protein, a transcription factor expressed in embryonic stem cells, is overexpressed in tumor development. Although studies investigating the function of NANOG in cancer have shown that it plays several roles, such as in cell proliferation, invasion and metastasis, the overall function of NANOG in cancer cells has remained elusive. In the present study, NANOG expression in oral squamous cell carcinoma (OSCC) was examined to determine its potential clinical significance. The expression of NANOG protein was assessed in 60 patients with OSCC by immunohistochemistry, and its correlation with clinicopathological factors and metastasis was evaluated. NANOG protein levels in human OSCC cell lines were determined by western blotting and immunofluorescence staining. NANOG protein expression was identified in 52 cases (86.7%) and expression levels were higher in primary foci of poorly differentiated OSCC than in those of well-differentiated OSCC, indicating that NANOG expression is associated with OSCC differentiation. Regardless of the differentiation levels of primary foci, NANOG expression levels in metastatic foci were extremely high. In addition, NANOG expression in metastatic foci was maintained at high levels following preoperative adjuvant therapy. Furthermore, NANOG protein was detected at an identical level in human OSCC cell lines. These data indicate that NANOG-expressing OSCC cells tend to metastasize and that metastatic tumors expressing NANOG may be resistant to preoperative adjuvant therapy, including chemoradiation. Thus, assessment of NANOG expression may assist the strategy for treatment of OSCC metastasis.
authors.affiliation: Graduate School of Dentistry, Osaka Dental University, Hirakata, Osaka 573-1121, Japan ; Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan ; Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, Hirakata, Osaka 573-1121, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan ; Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, Hirakata, Osaka 573-1121, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ohnishi
authors.affiliation: Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, Hirakata, Osaka 573-1121, Japan ; Department of Dentistry and Maxillofacial Surgery, Osaka Red Cross Hospital, Osaka 543-8555, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Oral Pathology, Osaka Dental University, Hirakata, Osaka 573-1121, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Wato
authors.affiliation: Oral Pathology, Osaka Dental University, Hirakata, Osaka 573-1121, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, Hirakata, Osaka 573-1121, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kakudo
authors.affiliation: Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Nozaki
keywords: NANOG; differentiation; metastasis; oral squamous cell carcinoma; preoperative adjuvant therapy