Hypoxia enhances stemness of cancer stem cells in glioblastoma: an in vitro study

Int J Med Sci. 2013;10(4):399-407. doi: 10.7150/ijms.5407. Epub 2013 Feb 21.

Abstract

Objective: To investigate the relationship between hypoxia and in vitro "stemness" of cancer stem cells (CSCs).

Methods: U87 cells, U251 cells and primary glioma cells (n=3) experienced hypoxia. Transmission electron microscopy was done to detect the ultrastructure of these cancer cells; MTT assay to detect the cell growth; flow cytometry to detect cell cycle and CD133 expression; Transwell chamber assay was carried out to detect the cell migration; colony-forming assay to detect the colony-forming efficiency; real-time quantitative PCR and Western blot were carried out to detect the mRNA and protein expression of markers of stem cells and their differentiation, respectively.

Results: Hypoxia maintained the undifferentiated state of primary glioma cells, slowed down the growth of glioma cells which were in a relatively quiescent stage, increased the colony forming efficiency and migration of glioma cells, and elevated the expression of markers of stem cells, but the expression of markers for stem cell differentiation was reduced after hypoxia treatment.

Conclusion: Hypoxia may induce the "dedifferentiation" of differentiated glioma cells which then acquire the stemness.

Keywords: Cancer stem cell; Gioblastoma; Hypoxia; Invasiveness.; Stemness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Antigens, CD
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Dedifferentiation / drug effects
  • Cell Dedifferentiation / genetics*
  • Cell Hypoxia / genetics*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma / metabolism
  • Glioma / pathology
  • Glycoproteins
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
  • In Vitro Techniques
  • Neoplasm Invasiveness / genetics
  • Neoplastic Stem Cells / cytology*
  • Neoplastic Stem Cells / metabolism
  • Oxygen / pharmacology*
  • Peptides

Substances

  • AC133 Antigen
  • Antigens, CD
  • Glycoproteins
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • PROM1 protein, human
  • Peptides
  • Oxygen