Identification and Characterization of Cancer Stem Cells from Head and Neck Squamous Cell Carcinoma Cell Lines

Abstract

Background/Aims: Head and neck squamous cell carcinoma (HNSCC) ranks sixth worldwide for tumor-related mortality. A subpopulation of tumor cells, termed cancer stem cells (CSCs), has the ability to support cancer growth. Therefore, profiling CSC-enriched populations could be a reliable tool to study cancer biology. Methods: We performed phenotypic characterization of 7 HNSCC cell lines and evaluated the presence of CSCs. CSCs from Hep-2 cell line and HNSCC primary cultures were enriched through sphere formation and sphere-forming cells have been characterized both in vitro and in vivo. In addition, we investigated the expression levels of Nicotinamide N-methyltransferase (NNMT), an enzyme overexpressed in several malignancies. Results: CSC markers were markedly expressed in Hep-2 cell line, which was found to be highly tumorigenic. CSC-enriched populations displayed increased expression of CSC markers and a strong capability to form tumors in vivo. We also found an overexpression of CSC markers in tumor formed by CSC-enriched populations. Interestingly, NNMT levels were significantly higher in CSC-enriched populations compared with parental cells. Conclusion: Our study provides an useful procedure for CSC identification and enrichment in HNSCC. Moreover, results obtained seem to suggest that CSCs may represent a promising target for an anticancer therapy.

Cancer Stem Cells in Oral Cavity Squamous Cell Carcinoma: A Review

“…In BMSCC, SOX2 is expressed within the tumor nests, the peritumoral stroma and the endothelium of the microvessels within the peritumoral stroma (29). In OCSCC and oropharyngeal SCC cell lines, SOX2 is overexpressed in CSCs compared to the parental cell population (37). In OTSCC, SOX2 is expressed by cells that also express SALL4, NANOG, phosphorylated STAT3 (pSTAT3), and CD44 (30).…”

“…In BMSCC, NANOG is expressed in cells within the tumor nests and the peritumoral stroma (29). In OCSCC and oropharyngeal SCC cell lines, NANOG is overexpressed in the CSC population compared to the parental population (37). Similarly in lip SCC, NANOG is expressed by three distinct putative CSC subpopulations, both within the tumor nests and the peritumoral stroma (42).…”

Influence of CD133+ expression on patients' survival and resistance of CD133+ cells to anti-tumor reagents in gastric cancer

“…The bFGF is known to promote the asymmetric division of neural stem cells, which are self-renewable and responsive to EGF. In the presence of EGF, EGF-responsive stem cells are self-replicative to produce secondary bFGF-responsive neural stem cells through mitosis and asymmetric division [8,33,34]. Singh et al isolated sphere cells from neuroepithelial tumor using serum-free culture media [8].…”

“…Moreover, tumor stem cells have been identified in colon and liver cancer [33,34]. Selected CD133 + cells, more proliferative than CD133 -cells, could be maintained, which suggested that differentiating tumor cells became apoptotic in the serum-free floating culture supplemented with growth factors.…”

Nicotinamide N-Methyltransferase Suppression Participates in Nickel-Induced Histone H3 Lysine9 Dimethylation in BEAS-2B Cells

“…NNMT expression has been shown to correlate with the migration, invasion, proliferation and survival of cancer cells [16-18]. Over-expression of NNMT in cancer cells resulted in hypomethylated histones by altering the cellular SAM/SAH ratio [19].…”