Abstract
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. 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. 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. 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.
Highlights
Oral squamous cell carcinoma (OSCC), like many solid tumors, contains a heterogeneous population of cancer cells
To further investigate the role of these two stemness/selfrenewal genes Oct-4 and Nanog in stem-like cells derived from OSCC, we firstly showed significant phenotypic differences between parental OSCC and derived oral cancer stem-like cells (OC-SLC) being cultured under defined serum-free medium containing basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF)
In contrast to OSCC, less and smaller sphere-like bodies were enriched from normal human oral keratinocytes (NHOK) cells under the serum-free medium culture
Summary
Oral squamous cell carcinoma (OSCC), like many solid tumors, contains a heterogeneous population of cancer cells. Results: Enriched OC-SLC highly expressed the stem/progenitor cell markers and ABC transporter gene (Oct-4, Nanog, CD117, Nestin, CD133, and ABCG2) and displayed induced differentiation abilities and enhanced migration/invasion/malignancy capabilities in vitro and in vivo. Expression of stemness markers (Nanog/Oct-4/CD133) contradicts the survival prognosis of OSCC patients. The side populations of tumor tissues or cancer cells, which may cause chemoresistance, display intracellular Hoechst 33342 exclusion in vitro and is isolated and characterized as CSC (14 – 17). The sphere body formation of CSC is enriched under the cultivation of defined serum-free medium with growth factors from individual solid tumors or cancer cells (19 – 21) where the serum-free culture condition helps maintain the CSC undifferentiated [19]
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