title: Cancer stem cells: mediators of tumorigenesis and metastasis in head and neck squamous cell carcinoma.
abstract: BACKGROUND
  Cancer stem cells (CSCs) represent a subpopulation of cells responsible for tumor growth. Their role in head and neck squamous cell carcinoma (HNSCC) tumorigenesis and metastasis remains uncertain.
  
  
  METHODS
  Wound healing and an orthotopic animal model were used to study cells expressing the CSC phenotype (CD44(high) and aldehyde dehydrogenase [ALDH](+)) and assess mobility, tumorigenesis, and metastasis. A prospective collection of 40 patient-derived primary HNSCC specimens were analyzed for CSC-proportion compared to clinical variables.
  
  
  RESULTS
  CSCs exhibited significantly faster wound closure and greater tumorigenesis and regional metastasis in vivo than non-CSCs. In primary patient tumors, size and advanced stage were correlated with elevated proportion of CSCs, however, not with survival.
  
  
  CONCLUSIONS
  HNSCC stem cells mediate tumorigenesis and regional metastasis in vivo. In primary patient tumors, CSC-proportion was associated with tumor size and stage, but not with metastatic spread or survival. CSC burden alone may only represent a minor variable in understanding CSCs and metastasis.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Chinn
authors.forename: Owen A
authors.initials: OA
authors.lastname: Darr
authors.forename: John H
authors.initials: JH
authors.lastname: Owen
authors.forename: Emily
authors.initials: E
authors.lastname: Bellile
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: McHugh
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Spector
authors.forename: Silvana M
authors.initials: SM
authors.lastname: Papagerakis
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Chepeha
authors.forename: Carol R
authors.initials: CR
authors.lastname: Bradford
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Carey
authors.forename: Mark E P
authors.initials: ME
authors.lastname: Prince
mesh_terms: D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D063646:Carcinogenesis; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology*; D002470:Cell Survival / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology*; D064593:Heterografts; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology; D009374:Neoplasms, Experimental; D014411:Neoplastic Stem Cells / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D012494:Sampling Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D018960:Hyaluronan Receptors; D000444:Aldehyde Dehydrogenase
keywords: CD44; animal model; cancer stem cells; head and neck squamous cell carcinoma; metastasis