Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma

Shih Hwa Chiou, Cheng Chia Yu, Chi Yang Huang, Shu Chun Lin, Chung Ji Liu, Tung Hu Tsai, Shiu Huey Chou, Chian Shiu Chien, Hung Hai Ku, Jeng Fan Lo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

580 Scopus citations

Abstract

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 sternness genes between enriched OC-SLC and parental OSCC was elucidated. Furthermore, immunohistochemical staining of sternness markers on OSCC patient tissues was examined to evaluate the association between sternness 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 sternness markers (Nanog/Oct-4/CD133) contradicts the survival prognosis of OSCC patients.

Original languageEnglish
Pages (from-to)4085-4095
Number of pages11
JournalClinical Cancer Research
Volume14
Issue number13
DOIs
StatePublished - 1 Jul 2008

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