CD133+ cells from medulloblastoma and PNET cell lines are more resistant to cyclopamine inhibition of the sonic hedgehog signaling pathway than CD133- cells.
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.
Enguita-Germán
Mónica
M
Brain Tumor Biology Unit, University of Navarra School of Sciences, Pamplona, Spain.
Schiapparelli
Paula
P
Rey
Juan A
JA
Castresana
Javier S
JS
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002528:Cerebellar Neoplasms / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008527:Medulloblastoma / Q000378:metabolism*; D018242:Neuroectodermal Tumors, Primitive / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D014704:Veratrum Alkaloids / Q000494:pharmacology*
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D053823:Hedgehog Proteins; C000606023:PROM1 protein, human; D010455:Peptides; D014704:Veratrum Alkaloids; C000541:cyclopamine