Tumor Biology

, Volume 31, Issue 5, pp 381–390

CD133+ cells from medulloblastoma and PNET cell lines are more resistant to cyclopamine inhibition of the sonic hedgehog signaling pathway than CD133− cells

  • Mónica Enguita-Germán
  • Paula Schiapparelli
  • Juan A. Rey
  • Javier S. Castresana
Research Article

DOI: 10.1007/s13277-010-0046-4

Cite this article as:
Enguita-Germán, M., Schiapparelli, P., Rey, J.A. et al. Tumor Biol. (2010) 31: 381. doi:10.1007/s13277-010-0046-4


CD133 has recently been used as a reliable marker for brain tumor stem cells isolation. Sonic hedgehog (SHH) is implicated in medulloblastoma and central primitive neuroectodermal tumor (cPNET) formation. It has recently been suggested a role for the EWS/FLI1 fusion protein—typical of pPNET—in the upregulation of GLI1 and PTCH1 genes. Cyclopamine inhibits the SHH pathway in medulloblastoma cell lines, but its effect on cPNET and pPNET cell lines has not been well established yet. Our purpose was to study the effect of cyclopamine on medulloblastoma and PNET cell lines and to analyze whether CD133 expression might be able to modify this effect. We analyzed gene expression, cell viability, apoptosis, and tumorigenic capability before and after cyclopamine treatment in CD133 high-expressing and CD133 low-expressing cell lines. All medulloblastoma and PNET cell lines displayed an inhibitory effect on the expression of SHH pathway genes, on viability, and on tumorigenic potential after treatment. Nevertheless, CD133 expression made the cells more resistant to cyclopamine inhibition. These results open new doors to the understanding of CD133+ cancer stem cells as residual cells that might be responsible for treatment resistance.


Sonic hedgehogCyclopamineCD133MedulloblastomaPNETEWS/FLI1



brain tumor stem cell


central nervous system


central primitive neuroectodermal tumor


external granular layer


granule cell precursor


neural stem cell


peripheral primitive neuroectodermal tumor


sonic hedgehog

Supplementary material

13277_2010_46_MOESM1_ESM.doc (27 kb)
ESM 1(DOC 27 kb)

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2010

Authors and Affiliations

  • Mónica Enguita-Germán
    • 1
  • Paula Schiapparelli
    • 1
  • Juan A. Rey
    • 2
  • Javier S. Castresana
    • 1
    • 3
  1. 1.Brain Tumor Biology UnitUniversity of Navarra School of SciencesPamplonaSpain
  2. 2.Research UnitLa Paz University HospitalMadridSpain
  3. 3.Unidad de Biología de Tumores Cerebrales, CIFAUniversidad de NavarraPamplonaSpain