Analysis of stemness gene expression and CD133 abnormal methylation in neuroblastoma cell lines
Fecha
2010Autor
Versión
Acceso abierto / Sarbide irekia
Tipo
Artículo / Artikulua
Versión
Versión publicada / Argitaratu den bertsioa
Impacto
|
10.3892/or_00000993
Resumen
Neuroblastoma is the most common extracranial
solid tumor in children, accounting for up to 10% of all
childhood malignancies. Cellular heterogeneity is a hallmark
of this embryonal cancer, as distinct neural crest lineages can
be found within the same tumor sample. The aim of our study
was to investigate the presence of a subpopulation of immature
cells with features of cancer-like stem cells in ...
[++]
Neuroblastoma is the most common extracranial
solid tumor in children, accounting for up to 10% of all
childhood malignancies. Cellular heterogeneity is a hallmark
of this embryonal cancer, as distinct neural crest lineages can
be found within the same tumor sample. The aim of our study
was to investigate the presence of a subpopulation of immature
cells with features of cancer-like stem cells in 10 neuroblastoma
cell lines. RT-PCR and flow cytometry were
performed in order to analyze different kinds of ‘stemness
genes’ such as: NESTIN (NES), CD133, SOX-2, BMI1, c-KIT,
MELK1, MUSASHI-1 (MSI1), FAS, CD44 and VIMENTIN
(VIM). In addition, glial and neuronal markers such as
NCAM1, GFAP and B-TUBULIN III (TUBB3) were
analyzed. Epigenetic changes within the CD133 (Prominin-1)
gene promoter were also analyzed. Neuroblastoma cell lines
showed a particular pattern of expression, suggesting the
presence of an immature cancer stem cell-like subpopulation.
The CD133 protein, commonly used to enrich putative cancer
propagating stem cell-like populations in different kinds of
solid tumors, presented a half-methylated DNA state in 7 of
the 12 neuroblastoma cell lines analyzed. An increase in
RNA and protein levels of CD133 was achieved following
demethylation by assays using 5-aza-2'-deoxycytidine
(5-Aza-dC). Since cancer stem cells are believed to be
responsible for tumor metastasis, escape from anticancer
therapies and disease relapse, their therapeutic targeting and
analysis is crucial in neuroblastoma. Moreover, the regulation
of CD133 by epigenetic changes may provide an innovative
mechanism of CD133 expression as its regulation still
remains unclear. [--]
Materias
Neuroblastoma,
CD133,
Epigenetics,
Neural stem cells
Editor
Spandidos Publications
Publicado en
Oncology reports, 24: 1355-1362, 2010
Departamento
Universidad Pública de Navarra. Departamento de Ciencias de la Salud /
Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila
Versión del editor
Entidades Financiadoras
This study was supported in part by grants from the Departmento de Salud
del Gobierno de Navarra (9/07), Caja Navarra (08/13912), and
Fundación Universitaria de Navarra, Pamplona; and Fondo
de Investigación Sanitaria (PI081849), Madrid.