p75 neurotrophin receptor: A potential surface marker of tongue squamous cell carcinoma stem cells

The present study detected p75 neurotrophin receptor (p75(NTR)) expression in tongue squamous cell carcinoma (TSCC) cell lines, in order to define the biological properties of p75(NTR+) cells and to confirm the use of p75(NTR+) as a surface marker for TSCC stem cells. p75(NTR+) cells were separated from Tca-8113 and CAL-27 TSCC cells by fluorescence-activated cell sorting. Colony formation, MTT and scratch assays, and a tumorigenicity analysis were performed to measure self-renewal and proliferation, multidirectional differentiation, and tumorigenicity of p75(NTR+) cells. p75(NTR+) cells comprised 3.1 and 1.9% of Tca-8113 and CAL-27 cells (mean of three experiments), respectively, and were more able to form colonies compared with non-sorted cells (P<0.01). In addition, the proportion of p75(NTR+) cells generated from monoclonal p75(NTR+) cells decreased to 14.5 (Tca-8113) and 5.8% (CAL-27) of cells within 2 weeks, thus suggesting that p75(NTR+) cells are able to generate p75(NTR+) and p75(NTR−) cells. Furthermore, p75(NTR+) cells exhibited increased proliferation, as evidenced by MTT assay (P<0.01) and had greater metastatic ability according to the scratch assay (P<0.01), compared with non-sorted cells. p75(NTR+) cells also exhibited a greater tumorigenic capacity compared with non-sorted cells. In conclusion, p75(NTR+) cells isolated from TSCC cell lines possess the characteristics of cancer stem cells; therefore, p75(NTR) may be considered a useful surface marker for the identification of TSCC stem cells.