Genetics and biology of medulloblastoma/PNET cell lines: Role of CD133 brain tumor stem cell marker

• Autores: Mónica Enguita Germán
• Directores de la Tesis: Francisco Javier Sáez Castresana (dir. tes.)
• Lectura: En la Universidad de Navarra ( España ) en 2009
• Idioma: español
• Tribunal Calificador de la Tesis: María Jesús López Zabalza (presid.), Miguel-Ángel Idoate (secret.), Silvia Nicolás Alonso (voc.), José Ángel Aguirre Gómez (voc.), Miguel Martorell Cebollada (voc.)
• Materias:
  • Ciencias de la vida
    • Biología celular
    • Genética
    • Biología molecular
• Texto completo no disponible (Saber más ...)
• Resumen

  • Medulloblastoma (MB) and cPNET are caused by alterations in the development of the CNS. The characteristics of these tumors fit with the cancer stem cell theory. Cancer stem cells have been detected in tumors and in cell lines. In MB, these cells are recognized by expression of the CD133 marker. So, any improvement that lead us to a better knowledge about the upstream and downstream regulation of CD133 might be important for the development of better therapeutic strategies. We selected four MB cell lines, one cPNET cell line and one pPNET cell line as a reference of a tumor with neuroectodermal origin but ocurring in non-neural tissues. We characterized the cell lines at the genetic, epigenetic and biological levels, making an especial effort on the study of CD133 as a central molecule. Regarding CD133 expression, a high-expressing group and a low-expressing group of cell lines were determined, the latter due to hypermethylation. Neurospheres displayed an increment in the tumorigenity potential and an enrichment in the number of CD133+ cells, but only in the CD133 low-expressing group of cell lines. The Shh pathway was completely activated in all cell lines, even so, the CD133 low-expressing group was the most sensitive one to the cyclopamine treatment. The number of CD133+ cells increased after infection with SOX2 lentivirus. We consider CD133 expression as an important factor to be taken into account since it modifies biological and therapeutical behaviors. CD133 expression seems to be regulated by promoter methylation and by SOX2 transcription factor expression.