Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer

Biochem Biophys Res Commun. 2009 Jul 31;385(3):307-13. doi: 10.1016/j.bbrc.2009.05.048. Epub 2009 May 18.

Abstract

Aldehyde dehydrogenase 1 (ALDH1) has been considered to be a marker for cancer stem cells. However, the role of ALDH1 in head and neck squamous cell carcinoma (HNSCC) has yet to be determined. In this study, we isolated ALDH1-positive cells from HNSCC patients and showed that these HNSCC-ALDH1+ cells displayed radioresistance and represented a reservoir for generating tumors. Based on microarray findings, the results of Western blotting and immunofluorescent assays further confirmed that ALDH1+-lineage cells showed evidence of having epithelial-mesenchymal transition (EMT) shifting and endogenously co-expressed Snail. Furthermore, the knockdown of Snail expression significantly decreased the expression of ALDH1, inhibited cancer stem-like properties, and blocked the tumorigenic abilities of CD44+CD24(-)ALDH1+ cells. Finally, in a xenotransplanted tumorigenicity study, we confirmed that the treatment effect of chemoradiotherapy for ALDH1+ could be improved by Snail siRNA. In summary, it is likely that ALDH1 is a specific marker for the cancer stem-like cells of HNSCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aldehyde Dehydrogenase / biosynthesis*
  • Aldehyde Dehydrogenase / genetics
  • Aldehyde Dehydrogenase 1
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / enzymology*
  • Female
  • Gene Knockdown Techniques
  • Head and Neck Neoplasms / enzymology*
  • Humans
  • Isoenzymes / biosynthesis*
  • Isoenzymes / genetics
  • Male
  • Mesenchymal Stem Cells / enzymology*
  • Middle Aged
  • Neoplastic Stem Cells / enzymology*
  • Oligonucleotide Array Sequence Analysis
  • Retinal Dehydrogenase
  • Snail Family Transcription Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tumor Cells, Cultured

Substances

  • Aldehyde Dehydrogenase 1
  • Biomarkers, Tumor
  • Isoenzymes
  • Snail Family Transcription Factors
  • Transcription Factors
  • Aldehyde Dehydrogenase
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase