Genome-wide microarray expression and genomic alterations by array-CGH analysis in neuroblastoma stem-like cells.
Neuroblastoma has a very diverse clinical behaviour: from spontaneous regression to a very aggressive malignant progression and resistance to chemotherapy. This heterogeneous clinical behaviour might be due to the existence of Cancer Stem Cells (CSC), a subpopulation within the tumor with stem-like...
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doaj-57d88bd5e3cb4e9fbb770a4e543a02272020-11-25T01:28:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01911e11310510.1371/journal.pone.0113105Genome-wide microarray expression and genomic alterations by array-CGH analysis in neuroblastoma stem-like cells.Raquel OrdóñezGabriel Gallo-OllerSoledad Martínez-SotoSheila LegarraNoémie Pata-MerciJustine GueganGiselle DanglotAlain BernheimBárbara MeléndezJuan A ReyJavier S CastresanaNeuroblastoma has a very diverse clinical behaviour: from spontaneous regression to a very aggressive malignant progression and resistance to chemotherapy. This heterogeneous clinical behaviour might be due to the existence of Cancer Stem Cells (CSC), a subpopulation within the tumor with stem-like cell properties: a significant proliferation capacity, a unique self-renewal capacity, and therefore, a higher ability to form new tumors. We enriched the CSC-like cell population content of two commercial neuroblastoma cell lines by the use of conditioned cell culture media for neurospheres, and compared genomic gains and losses and genome expression by array-CGH and microarray analysis, respectively (in CSC-like versus standard tumor cells culture). Despite the array-CGH did not show significant differences between standard and CSC-like in both analyzed cell lines, the microarray expression analysis highlighted some of the most relevant biological processes and molecular functions that might be responsible for the CSC-like phenotype. Some signalling pathways detected seem to be involved in self-renewal of normal tissues (Wnt, Notch, Hh and TGF-β) and contribute to CSC phenotype. We focused on the aberrant activation of TGF-β and Hh signalling pathways, confirming the inhibition of repressors of TGF-β pathway, as SMAD6 and SMAD7 by RT-qPCR. The analysis of the Sonic Hedgehog pathway showed overexpression of PTCH1, GLI1 and SMO. We found overexpression of CD133 and CD15 in SIMA neurospheres, confirming that this cell line was particularly enriched in stem-like cells. This work shows a cross-talk among different pathways in neuroblastoma and its importance in CSC-like cells.http://europepmc.org/articles/PMC4231109?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Raquel Ordóñez Gabriel Gallo-Oller Soledad Martínez-Soto Sheila Legarra Noémie Pata-Merci Justine Guegan Giselle Danglot Alain Bernheim Bárbara Meléndez Juan A Rey Javier S Castresana |
spellingShingle |
Raquel Ordóñez Gabriel Gallo-Oller Soledad Martínez-Soto Sheila Legarra Noémie Pata-Merci Justine Guegan Giselle Danglot Alain Bernheim Bárbara Meléndez Juan A Rey Javier S Castresana Genome-wide microarray expression and genomic alterations by array-CGH analysis in neuroblastoma stem-like cells. PLoS ONE |
author_facet |
Raquel Ordóñez Gabriel Gallo-Oller Soledad Martínez-Soto Sheila Legarra Noémie Pata-Merci Justine Guegan Giselle Danglot Alain Bernheim Bárbara Meléndez Juan A Rey Javier S Castresana |
author_sort |
Raquel Ordóñez |
title |
Genome-wide microarray expression and genomic alterations by array-CGH analysis in neuroblastoma stem-like cells. |
title_short |
Genome-wide microarray expression and genomic alterations by array-CGH analysis in neuroblastoma stem-like cells. |
title_full |
Genome-wide microarray expression and genomic alterations by array-CGH analysis in neuroblastoma stem-like cells. |
title_fullStr |
Genome-wide microarray expression and genomic alterations by array-CGH analysis in neuroblastoma stem-like cells. |
title_full_unstemmed |
Genome-wide microarray expression and genomic alterations by array-CGH analysis in neuroblastoma stem-like cells. |
title_sort |
genome-wide microarray expression and genomic alterations by array-cgh analysis in neuroblastoma stem-like cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
Neuroblastoma has a very diverse clinical behaviour: from spontaneous regression to a very aggressive malignant progression and resistance to chemotherapy. This heterogeneous clinical behaviour might be due to the existence of Cancer Stem Cells (CSC), a subpopulation within the tumor with stem-like cell properties: a significant proliferation capacity, a unique self-renewal capacity, and therefore, a higher ability to form new tumors. We enriched the CSC-like cell population content of two commercial neuroblastoma cell lines by the use of conditioned cell culture media for neurospheres, and compared genomic gains and losses and genome expression by array-CGH and microarray analysis, respectively (in CSC-like versus standard tumor cells culture). Despite the array-CGH did not show significant differences between standard and CSC-like in both analyzed cell lines, the microarray expression analysis highlighted some of the most relevant biological processes and molecular functions that might be responsible for the CSC-like phenotype. Some signalling pathways detected seem to be involved in self-renewal of normal tissues (Wnt, Notch, Hh and TGF-β) and contribute to CSC phenotype. We focused on the aberrant activation of TGF-β and Hh signalling pathways, confirming the inhibition of repressors of TGF-β pathway, as SMAD6 and SMAD7 by RT-qPCR. The analysis of the Sonic Hedgehog pathway showed overexpression of PTCH1, GLI1 and SMO. We found overexpression of CD133 and CD15 in SIMA neurospheres, confirming that this cell line was particularly enriched in stem-like cells. This work shows a cross-talk among different pathways in neuroblastoma and its importance in CSC-like cells. |
url |
http://europepmc.org/articles/PMC4231109?pdf=render |
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