Aldehyde dehydrogenase 1, a functional marker for identifying cancer stem cells in human nasopharyngeal carcinoma

Cancer Lett. 2013 Apr 28;330(2):181-9. doi: 10.1016/j.canlet.2012.11.046. Epub 2012 Dec 5.

Abstract

Aldehyde dehydrogenase 1 (ALDH1) activity has now been employed successfully as a cancer stem cells (CSCs) marker in various tumors. We wanted to investigate whether ALDH1 can be used as a putative CSCs marker and a powerful prognostic factor in nasopharyngeal carcinoma (NPC). Here, we isolated ALDH1-positive cells from human NPC cell lines (5-8F and CNE2) and found that ALDH1-positive cancer cells grew faster and had higher clone formation efficiency (0.435±0.15; 0.431±0.025 vs. 0.131±0.007; 0.121±0.126), differentiation capability and had higher migration (233.00±5.29; 228.60±9.34 vs. 123.20±7.70 vs. 97.20±6.61) than those of ALDH1-negative cancer cells in vitro. In addition, ALDH1- positive cancer cells formed significantly more tumor spheres. Our in vivo experiments showed that only 5×10(3) ALDH1-positive NPC cells were required to induce tumors. Notably, ALDH1-positive cells are enriched in the side-population (SP) cells, and stem cells-like genes OCT4, BMI1, KLF4 and SOX2 are preferentially expressed in ALDH1-positive cells. Immunohistochemical results showed that the expression of ALDH1 correlated significantly with T classification (P=0.011), N classification (P=0.005), M classification (P=0.002) and clinical stage (P=0.001). Interestingly, ALDH1 expression in the tumor correlated significantly with epithelial-mesenchymal transition (EMT) markers including vimentin expression and loss of E-cadherin (P=0.003 and 0.008, respectively). Furthermore, multivariate analyses showed that ALDH1 expression was an independent prognostic indicator (P=0.032). Taken together, for the first time, we demonstrate that ALDH1 could be a novel stem cells marker and a valuable predictor of poor survival NPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aldehyde Dehydrogenase 1 Family
  • Animals
  • Biomarkers
  • Carcinoma
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition
  • Female
  • Humans
  • Isoenzymes / analysis
  • Isoenzymes / physiology*
  • Kruppel-Like Factor 4
  • Male
  • Mice
  • Middle Aged
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / enzymology*
  • Nasopharyngeal Neoplasms / mortality
  • Nasopharyngeal Neoplasms / pathology
  • Neoplasm Staging
  • Neoplastic Stem Cells / enzymology*
  • Retinal Dehydrogenase / analysis
  • Retinal Dehydrogenase / physiology*

Substances

  • Biomarkers
  • Isoenzymes
  • KLF4 protein, human
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A1 protein, human
  • ALDH1A1 protein, mouse
  • Retinal Dehydrogenase