title: Neuroblastoma cells negative for CD44 possess tumor-initiating properties.
abstract: BACKGROUND
  CD44 has been linked to favorable prognosis in neuroblastoma and in the present study we investigate if it can be used to prospectively isolate neuroblastoma-initiating cells.
  
  
  METHODS
  To define the cancer-initiating properties of CD44 positive and negative cells, we FACS-sorted the SK-N-SH neuroblastoma cell line on the basis of CD44 expression and proceeded to phenotypically and molecularly characterize the two cell subpopulations.
  
  
  RESULTS
  We found that CD44 defines two morphologically distinctive cell populations with different adhesion molecule profiles, and that CD44 negative cells expressed higher levels of the neuroblastoma-initiating cell marker CD24. When inoculated subcutaneously into NOD/SCID animals, the CD44 negative cells were capable of tumor formation and organ infiltration, clearly demonstrating an inverse correlation of CD44 expression and neuroblastoma metastases formation. Gene expression analysis revealed that CD44 defines molecularly discrete cell types with the CD44 negative cells expressing proteins associated with uncontrolled cell cycle progression, immune evasion and a reduced capacity to undergo apoptosis.
  
  
  CONCLUSIONS
  Collectively, our findings show that CD44 negative neuroblastoma cells possess all the phenotypic and molecular features required for a cancer-initiating cell.
authors.affiliation: Cell and Gene Therapy Lab, Basic Research II, Biomedical Research Foundation of the Academy of Athens, Greece. esiapati@bioacademy.gr
authors.forename: Elena K
authors.initials: EK
authors.lastname: Siapati
authors.forename: Erasmia
authors.initials: E
authors.lastname: Rouka
authors.forename: Despina
authors.initials: D
authors.lastname: Kyriakou
authors.forename: George
authors.initials: G
authors.lastname: Vassilopoulos
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D048430:Cell Shape; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D061206:Neoplasm Micrometastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D040521:Subcutaneous Tissue / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors