Cancer stem cells: mediators of tumorigenesis and metastasis in head and neck squamous cell carcinoma

Head Neck. 2015 Mar;37(3):317-26. doi: 10.1002/hed.23600. Epub 2014 Mar 25.

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.

Conclusion: 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.

Keywords: CD44; animal model; cancer stem cells; head and neck squamous cell carcinoma; metastasis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aldehyde Dehydrogenase / metabolism*
  • Animals
  • Biomarkers, Tumor / metabolism
  • Carcinogenesis
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology*
  • Cell Survival / physiology
  • Cell Transformation, Neoplastic / pathology
  • Female
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology*
  • Heterografts
  • Humans
  • Hyaluronan Receptors / metabolism*
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Metastasis / pathology
  • Neoplasms, Experimental
  • Neoplastic Stem Cells / pathology*
  • Prognosis
  • Prospective Studies
  • Sampling Studies
  • Squamous Cell Carcinoma of Head and Neck
  • Survival Analysis
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • Hyaluronan Receptors
  • Aldehyde Dehydrogenase