H+-myo-Inositol Transporter SLC2A13 as a Potential Marker for Cancer Stem Cells in an Oral Squamous Cell Carcinoma

D.      G. Lee; J.-H.      Lee; B.      K. Choi; M.-J.      Kim; S.-M.      Kim; K.      S. Kim; K.      Chang; S.      H. Park; Y.-S.      Bae; B.      S. Kwon

Abstract

Cancer Stem Cells (CSCs) from tumors of different phenotypes possess a marked capacity for proliferation, self-renewal, and differentiation. They also play a critical role in cancer recurrence. Although CSC has been regarded as a new target for cancer therapy, the fundamental questions in the CSC study have not been resolved mainly due to the lack of proper CSC markers. To find new CSC markers for oral squamous cell carcinoma (OSCC), we cultured the primary tumor cells from OSCC patients the regular culture condition and the sphere-forming culture condition to enrich primary tumor cells and potential CSCs. We compared gene expression profiles between sphere-forming and non-forming cells, thus identifying that 23 membrane protein-coding genes were over-expressed in the sphere-forming cells. Among them, 8 belonged to the solute carrier (SLC) protein family. H+-myo-inositol transporter SLC2A13 and monocarbohydrate transporter SLC16A6 genes that were consistently increased in the sphere-forming cells in the primary cultures of OSCC samples. Confocal microscopy revealed that SLC2A13-expressing cells were embedded in the limited areas of tumor tissue as a cluster, while SLC16A6 was uniformly detected in hyperplastic epithelium. Moreover, SLC2A13 an expression was induced in human breast adenocarcinoma MCF7 cells after serum starvation. Taken together, our results suggest that SLC2A13 can be a potential markers for CSC in various tumors.

Keywords: Hypoxia, microarray, oral squamous cell carcinoma, solute carrier protein family gene, sphere-forming cells, starvation, Cancer stem cells, 4,6-diamidino-2-phenylindole, Dulbecco's modified Eagle's medium/F-12, Fluorescein isothiocyanate, Multi-drug resistant, Solute carrier protein