title: The effects of CD44 down-regulation on stem cell properties of head and neck cancer cell lines.
abstract: BACKGROUND
  There is now substantial evidence that only a subpopulation of cells in solid cancers is able to sustain tumour growth and to re-initiate new tumours. Various cancers and cancer-derived cell lines, including head and neck squamous cell carcinomas (HNSCC), have a subpopulation of cancer stem cells (CSCs), marked by high levels of expression of the CD44 adhesion molecule. However, it has been unclear whether, in addition to acting as a marker, CD44 has functions that directly influence stem cell properties. The aim of this study was to investigate the role of CD44 in the maintenance of the CSC population in HNSCC cell lines.
  
  
  METHODS
  CD44 was down-regulated either by treating cultures with 1 mM sodium butyrate or by the more specific method of knockdown with siRNAs directed against CD44. Changes in CD44 expression levels were assessed at the mRNA and protein levels, and the effects of CD44 down-regulation on cell proliferation and on the fate of the CSC subpopulations were assessed.
  
  
  RESULTS
  Reduced CD44 expression resulted in a decreased rate of population expansion, both initially and on repassage, and there was an alteration in colony morphologies indicative of stem cell loss. Down-regulation of CD44 also led to reduced expression of Oct4A, an alternative marker of CSCs.
  
  
  CONCLUSIONS
  The results suggest that CD44 has a functional role in maintaining stem cell properties in HNSCC cell lines and provides support for the concept that therapies targeting CD44, or its related signalling pathways, may allow development of more efficient treatment strategies.
authors.affiliation: Faculty of Dentistry, National University of Singapore, Singapore.
authors.forename: Fahad
authors.initials: F
authors.lastname: Kidwai
authors.forename: Daniela E
authors.initials: DE
authors.lastname: Costea
authors.forename: Iain
authors.initials: I
authors.lastname: Hutchison
authors.forename: Ian
authors.initials: I
authors.lastname: Mackenzie
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D020148:Butyric Acid / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002452:Cell Count; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis* / Q000187:drug effects / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000502:physiology*; D050814:Octamer Transcription Factor-3 / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020148:Butyric Acid
keywords: CD44; cancer stem cells; head and neck cancers