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The low‐affinity nerve growth factor receptor p75 NTR identifies a transient stem cell‐like state in oral squamous cell carcinoma cells
Author(s) -
Osman Tarig A.,
Parajuli Himalaya,
Sapkota Dipak,
Ahmed Israa A. H.,
Johannessen Anne Ch.,
Costea Daniela Elena
Publication year - 2015
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12251
Subject(s) - stem cell , biology , stem cell marker , microbiology and biotechnology , cell , cancer stem cell , cell culture , cancer research , immunology , genetics
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 p75 NTR . Objective To investigate the potential of p75 NTR 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 p75 NTR 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 p75NTR High cells exhibited statistically significant higher stem cell properties than p75NTR Low cells in all assays performed. Nevertheless, p75NTR Low subpopulation did also exhibit some stem cell features, but to a lesser extent. Propagation of p75NTR Low cells for several passages in culture showed that the expression of p75 NTR could rise spontaneously. This finding was also supported by the similar expression of p75 NTR by the xenografts generated by both subpopulations in NOD \ SCID IL 2Rg null mice. Conclusion p75 NTR can be used for isolating a subpopulation enriched for cells with stem cell‐like properties in OSCC. De novo generation of p75NTR High cells from p75NTR Low cells suggests either that there is another subpopulation with stem cell features within the p75NTR Low cells, or that the p75NTR Low cells can dedifferentiate due to a contextually regulated equilibrium between stem cell‐like cells and transit‐amplifying neoplastic progenitors.