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

Deric M Park1, Jinkyu Jung, Jimmy Masjkur

  • 1Department of Neurological Surgery, University of Virginia, Virginia, USA.

Scientific Reports
|February 9, 2013
PubMed

Insights

Cancer stem cells in Glioblastoma Multiforme tumors express neural stem cell markers. Inhibiting Hes3, a neural stem cell marker, via RNA interference offers a potential therapeutic strategy for glioblastoma.

Area of Science:

  • Neuro-oncology
  • Cancer Stem Cell Biology
  • Molecular Therapeutics

Background:

  • Glioblastoma Multiforme (GBM) tumors contain diverse cell populations, with cancer stem cells (CSCs) driving tumor regeneration.
  • CSCs in GBM share markers like nestin and Sox2 with non-cancerous neural stem cells (NSCs).
  • The transcription factor Hes3 is a known NSC marker, and its expression is regulated by Janus Kinase (JAK) activity.

Purpose of the Study:

  • To investigate the role and regulation of Hes3 in Glioblastoma Multiforme CSCs.
  • To explore the potential of targeting Hes3 as a therapeutic strategy for glioblastoma.

Main Methods:

  • Culturing Glioblastoma Multiforme cells expressing NSC markers.
  • Assessing Hes3 expression and its regulation by JAK signaling.
  • Performing Hes3 RNA interference (RNAi) experiments.
  • Transplanting cultured cells into immunocompromised mice to evaluate tumor recapitulation.

Main Results:

  • Hes3 is expressed in Glioblastoma Multiforme cultures that exhibit NSC markers.
  • These GBM cells can differentiate into neurons and glia and form tumors upon transplantation.
  • Similar to NSCs, JAK signaling inhibits Hes3 expression in GBM cells.
  • Hes3 RNA interference led to a reduction in the number of cultured glioblastoma cells.

Conclusions:

  • Hes3 is a functional marker in Glioblastoma Multiforme cancer stem cells.
  • The JAK-Hes3 pathway is conserved between neural stem cells and glioblastoma stem cells.
  • Targeting Hes3 through RNA interference presents a promising novel therapeutic avenue for glioblastoma treatment.

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