Hes3 regulates cell number in cultures from glioblastoma multiforme with stem cell characteristics

Sci Rep. 2013;3:1095. doi: 10.1038/srep01095. Epub 2013 Feb 5.

Abstract

Tumors exhibit complex organization and contain a variety of cell populations. The realization that the regenerative properties of a tumor may be largely confined to a cell subpopulation (cancer stem cell) is driving a new era of anti-cancer research. Cancer stem cells from Glioblastoma Multiforme tumors express markers that are also expressed in non-cancerous neural stem cells, including nestin and Sox2. We previously showed that the transcription factor Hes3 is a marker of neural stem cells, and that its expression is inhibited by JAK activity. Here we show that Hes3 is also expressed in cultures from glioblastoma multiforme which express neural stem cell markers, can differentiate into neurons and glia, and can recapitulate the tumor of origin when transplanted into immunocompromised mice. Similar to observations in neural stem cells, JAK inhibits Hes3 expression. Hes3 RNA interference reduces the number of cultured glioblastoma cells suggesting a novel therapeutic strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-2 / metabolism
  • Animals
  • Biomarkers / metabolism
  • Central Nervous System Neoplasms / drug therapy
  • Central Nervous System Neoplasms / metabolism
  • Central Nervous System Neoplasms / pathology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Embryonic Stem Cells / metabolism
  • Epidermal Growth Factor / pharmacology
  • Fibroblast Growth Factor 2 / pharmacology
  • Glioblastoma / drug therapy
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Janus Kinase 1 / metabolism
  • Janus Kinase 1 / pharmacology
  • Mice
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Phosphorylation
  • RNA, Small Interfering
  • Repressor Proteins
  • STAT3 Transcription Factor / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured

Substances

  • Angiopoietin-2
  • Biomarkers
  • DNA-Binding Proteins
  • HES3 protein, human
  • RNA, Small Interfering
  • Repressor Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Transcription Factors
  • Fibroblast Growth Factor 2
  • Epidermal Growth Factor
  • Janus Kinase 1