This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Chiou, S.-H. Articles by Lo, J.-F. PubMed PubMed Citation Articles by Chiou, S.-H. Articles by Lo, J.-F.

Positive Correlations of Oct-4 and Nanog in Oral Cancer Stem-Like Cells and High-Grade Oral Squamous Cell Carcinoma

Authors' Affiliations: Institutes of ¹ Oral Biology, ² Traditional Medicine, and ³ Anatomy and Cell Biology, National Yang-Ming University; ⁴ Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei; ⁵ Department of Education and Research, Taipei City Hospital; ⁶ Department of Oral and Maxillofacial Surgery, Mackay Memorial Hospital; ⁷ Department of Life Science, Fu-Jen University, Taipei, Taiwan, Republic of China and ⁸ Graduate Institute of Chinese Medical Science and Institute of Medical Science, China Medical University, Taichung, Taiwan, Republic of China

Requests for reprints: Jeng-Fan Lo, Institute of Oral Biology, National Yang-Ming University, No. 155, Section 2, Li-Nung Street, Taipei 11217, Taiwan, Republic of China. Phone: 886-2-28267222; Fax: 886-2-28264053; E-mail: jflo{at}ym.edu.tw.

Purpose: Oral squamous cell carcinoma (OSCC), like many solid tumors, contains a heterogeneous population of cancer cells. Recent data suggest that a rare subpopulation of cancer cells, termed cancer stem cells (CSC), is capable of initiating, maintaining, and expanding the growth of tumor. Identification and characterization of CSC from OSCC facilitates the monitoring, therapy, or prevention of OSCC.

Experimental Design: We enriched oral cancer stem-like cells (OC-SLC) through sphere formation by cultivating OSCC cells from established OSCC cell lines or primary cultures of OSCC patients within defined serum-free medium. Differential expression profile of stemness genes between enriched OC-SLC and parental OSCC was elucidated. Furthermore, immunohistochemical staining of stemness markers on OSCC patient tissues was examined to evaluate the association between stemness genes and prognosis of OSCC.

Results: Enriched OC-SLC highly expressed the stem/progenitor cell markers and ABC transporter gene (Oct-4, Nanog, CD117, Nestin, CD133, and ABCG2) and also displayed induced differentiation abilities and enhanced migration/invasion/malignancy capabilities in vitro and in vivo. Elevated expression of CD133 was shown in the enriched OC-SLC from OSCC patients' tumors. Positive correlations of Oct-4, Nanog, or CD133 expression on tumor stage were shown on 52 OSCC patient tissues. Kaplan-Meier analyses exhibited that Nanog/Oct-4/CD133 triple-positive patients predicted the worst survival prognosis of OSCC patients.

Conclusion: We enriched a subpopulation of cancer stem-like cell from OSCC by sphere formation. The enriched OC-SLC possesses the characteristics of both stem cells and malignant tumors. Additionally, expression of stemness markers (Nanog/Oct-4/CD133) contradicts the survival prognosis of OSCC patients.