The low-affinity nerve growth factor receptor p75NTR identifies a transient stem cell-like state in oral squamous cell carcinoma cells

Background Although several markers have been used for enrichment of cells with stem cell‐like properties in oral squamous cell carcinoma (OSCC), isolation of a pure subpopulation is still a challenging task. Normal oral and esophageal keratinocyte stem cells have been previously isolated using the low‐affinity nerve growth factor receptor p75NTR. Objective To investigate the potential of p75NTR as a marker for identification and isolation of oral cancer cells with stem cell‐like properties. Methods Subpopulations of cells with high or low expression of p75NTR were sorted from OSCC‐derived cells and compared for sphere/colony formation, in vivo tumor formation ability, expression of stem cell‐related molecules, cell cycle distribution and drug resistance. Results p75NTRHigh cells exhibited statistically significant higher stem cell properties than p75NTRLow cells in all assays performed. Nevertheless, p75NTRLow subpopulation did also exhibit some stem cell features, but to a lesser extent. Propagation of p75NTRLow cells for several passages in culture showed that the expression of p75NTR could rise spontaneously. This finding was also supported by the similar expression of p75NTR by the xenografts generated by both subpopulations in NOD\SCID IL2Rgnullmice. Conclusion p75NTR can be used for isolating a subpopulation enriched for cells with stem cell‐like properties in OSCC. De novo generation of p75NTRHigh cells from p75NTRLow cells suggests either that there is another subpopulation with stem cell features within the p75NTRLow cells, or that the p75NTRLow cells can dedifferentiate due to a contextually regulated equilibrium between stem cell‐like cells and transit‐amplifying neoplastic progenitors.