Hypoxia upregulates aldehyde dehydrogenase isoform 1 (ALDH1) expression and induces functional stem cell characteristics in human glioblastoma cells

Eric Soehngen, Andrea Schaefer, Julia Koeritzer, Velia Huelsmeyer, Claus Zimmer, Florian Ringel, Jens Gempt, Juergen Schlegel

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Aldehyde dehydrogenase 1 (ALDH1) has been used to isolate tumorigenic stem-like cells in a large number of tumors, including glioblastoma multiforme (GBM). We recently showed that human glioblastoma cells with high ALDH1 (ALDH1high) activity contain stem-cell-like characteristics. In the study reported here, we isolated established and primary human glioblastoma cells based on their ALDH1 expression. When tested for asymmetric division, only cells with ALDH1high expression were able to restore heterogeneous populations after a few days, whereas cells with ALDH1low levels could not. Most interestingly, the capacity of cells with ALDH1low levels to divide asymmetrically into cells with either ALDH1high or ALDH1low expression could be restored after exposure to hypoxic culture conditions. Consequently, we found neurosphere formation reinstated in posthypoxic, formerly ALDH1low, cells. The direct involvement of ALDH1 could be confirmed by ALDH1 small hairpin ribonucleic acid (shRNA) knockdown, suggesting ALDH1 as an intracellular marker for the identification and isolation of stem-like glioblastoma cells. In summary, we show that ALDH1 expression correlates well with asymmetric division capacity and tumor sphere formation. Furthermore, we demonstrated that hypoxic culture conditions induce and/or upregulate ALDH1 expression in established and primary GBM cell lines.

Original languageEnglish
Pages (from-to)247-256
Number of pages10
JournalBrain Tumor Pathology
Volume31
Issue number4
DOIs
StatePublished - 18 Oct 2014
Externally publishedYes

Keywords

  • Aldehyde dehydrogenase 1
  • Cell hypoxia
  • Glioblastoma
  • Neoplastic stem cells

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