title: The low-affinity nerve growth factor receptor p75NTR identifies a transient stem cell-like state in oral squamous cell carcinoma cells.
abstract: 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
  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 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 IL2Rg(null) mice.
  
  
  CONCLUSIONS
  p75NTR 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.
authors.affiliation: Gade Laboratory for Pathology, Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Global Public Health and Primary Care, Center for International Health, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Tarig A
authors.initials: TA
authors.lastname: Osman
authors.affiliation: Gade Laboratory for Pathology, Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Global Public Health and Primary Care, Center for International Health, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Himalaya
authors.initials: H
authors.lastname: Parajuli
authors.affiliation: Gade Laboratory for Pathology, Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Dipak
authors.initials: D
authors.lastname: Sapkota
authors.affiliation: Gade Laboratory for Pathology, Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Global Public Health and Primary Care, Center for International Health, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Israa A H
authors.initials: IA
authors.lastname: Ahmed
authors.affiliation: Gade Laboratory for Pathology, Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Anne Ch
authors.initials: ACh
authors.lastname: Johannessen
authors.affiliation: Gade Laboratory for Pathology, Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.|Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Daniela Elena
authors.initials: DE
authors.lastname: Costea
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D014408:Biomarkers, Tumor; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor
keywords: cancer stem cell; oral squamous cell carcinoma; p75NTR; plasticity; stochastic stem cell; tumor heterogeneity