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


METHODS
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.


CONCLUSIONS
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.
Chiou
Shih-Hwa
SH
Institutes of Oral Biology, Traditional Medicine, and Anatomy and Cell Biology, National Yang-Ming University, Taiwan, People's Republic of China.
Yu
Cheng-Chia
CC
Huang
Chi-Yang
CY
Lin
Shu-Chun
SC
Liu
Chung-Ji
CJ
Tsai
Tung-Hu
TH
Chou
Shiu-Huey
SH
Chien
Chian-Shiu
CS
Ku
Hung-Hai
HH
Lo
Jeng-Fan
JF
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000096:biosynthesis; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D000071317:Nanog Homeobox Protein; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology*; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis*; D010455:Peptides
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse