期刊
TUMOR BIOLOGY
卷 31, 期 5, 页码 381-390出版社
SAGE PUBLICATIONS LTD
DOI: 10.1007/s13277-010-0046-4
关键词
Sonic hedgehog; Cyclopamine; CD133; Medulloblastoma; PNET; EWS/FLI1
类别
资金
- Asociacion de Amigos de la Universidad de Navarra
- Departamento de Educacion del Gobierno de Navarra
- Departmento de Salud del Gobierno de Navarra [9/07]
- Caja Navarra [08/13912]
- Fundacion Universitaria de Navarra, Pamplona and Fondo de Investigacion Sanitaria, Madrid [PI081849]
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.
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