Characterization of human mesenchymal stem cells from ewing sarcoma patients. Pathogenetic implications.

<h4>Background</h4>Ewing Sarcoma (EWS) is a mesenchymal-derived tumor that generally arises in bone and soft tissue. Intensive research regarding the pathogenesis of EWS has been insufficient to pinpoint the early events of Ewing sarcomagenesis. However, the Mesenchymal Stem Cell (MSC) i...

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Autores principales:	Ana Teresa Amaral, Maria Cristina Manara, Dagmar Berghuis, José Luis Ordóñez, Michele Biscuola, Maria Angeles Lopez-García, Daniel Osuna, Enrico Lucarelli, Francesco Alviano, Arjan Lankester, Katia Scotlandi, Enrique de Álava
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/463f0eb937254aa4ba9bedb12bfa41eb
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spelling	oai:doaj.org-article:463f0eb937254aa4ba9bedb12bfa41eb2021-11-18T08:34:22ZCharacterization of human mesenchymal stem cells from ewing sarcoma patients. Pathogenetic implications.1932-620310.1371/journal.pone.0085814https://doaj.org/article/463f0eb937254aa4ba9bedb12bfa41eb2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24498265/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Ewing Sarcoma (EWS) is a mesenchymal-derived tumor that generally arises in bone and soft tissue. Intensive research regarding the pathogenesis of EWS has been insufficient to pinpoint the early events of Ewing sarcomagenesis. However, the Mesenchymal Stem Cell (MSC) is currently accepted as the most probable cell of origin.<h4>Materials and methods</h4>In an initial study regarding a deep characterization of MSC obtained specifically from EWS patients (MSC-P), we compared them with MSC derived from healthy donors (MSC-HD) and EWS cell lines. We evaluated the presence of the EWS-FLI1 gene fusion and EWSR1 gene rearrangements in MSC-P. The presence of the EWS transcript was confirmed by q-RT-PCR. In order to determine early events possibly involved in malignant transformation, we used a multiparameter quantitative strategy that included both MSC immunophenotypic negative/positive markers, and EWS intrinsic phenotypical features. Markers CD105, CD90, CD34 and CD45 were confirmed in EWS samples.<h4>Results</h4>We determined that MSC-P lack the most prevalent gene fusion, EWSR1-FLI1 as well as EWSR1 gene rearrangements. Our study also revealed that MSC-P are more alike to MSC-HD than to EWS cells. Nonetheless, we also observed that EWS cells had a few overlapping features with MSC. As a relevant example, also MSC showed CD99 expression, hallmark of EWS diagnosis. However, we observed that, in contrast to EWS cells, MSC were not sensitive to the inhibition of CD99.<h4>Conclusions</h4>In conclusion, our results suggest that MSC from EWS patients behave like MSC-HD and are phenotypically different from EWS cells, thus raising important questions regarding MSC role in sarcomagenesis.Ana Teresa AmaralMaria Cristina ManaraDagmar BerghuisJosé Luis OrdóñezMichele BiscuolaMaria Angeles Lopez-GarcíaDaniel OsunaEnrico LucarelliFrancesco AlvianoArjan LankesterKatia ScotlandiEnrique de ÁlavaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e85814 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ana Teresa Amaral Maria Cristina Manara Dagmar Berghuis José Luis Ordóñez Michele Biscuola Maria Angeles Lopez-García Daniel Osuna Enrico Lucarelli Francesco Alviano Arjan Lankester Katia Scotlandi Enrique de Álava Characterization of human mesenchymal stem cells from ewing sarcoma patients. Pathogenetic implications.
description	<h4>Background</h4>Ewing Sarcoma (EWS) is a mesenchymal-derived tumor that generally arises in bone and soft tissue. Intensive research regarding the pathogenesis of EWS has been insufficient to pinpoint the early events of Ewing sarcomagenesis. However, the Mesenchymal Stem Cell (MSC) is currently accepted as the most probable cell of origin.<h4>Materials and methods</h4>In an initial study regarding a deep characterization of MSC obtained specifically from EWS patients (MSC-P), we compared them with MSC derived from healthy donors (MSC-HD) and EWS cell lines. We evaluated the presence of the EWS-FLI1 gene fusion and EWSR1 gene rearrangements in MSC-P. The presence of the EWS transcript was confirmed by q-RT-PCR. In order to determine early events possibly involved in malignant transformation, we used a multiparameter quantitative strategy that included both MSC immunophenotypic negative/positive markers, and EWS intrinsic phenotypical features. Markers CD105, CD90, CD34 and CD45 were confirmed in EWS samples.<h4>Results</h4>We determined that MSC-P lack the most prevalent gene fusion, EWSR1-FLI1 as well as EWSR1 gene rearrangements. Our study also revealed that MSC-P are more alike to MSC-HD than to EWS cells. Nonetheless, we also observed that EWS cells had a few overlapping features with MSC. As a relevant example, also MSC showed CD99 expression, hallmark of EWS diagnosis. However, we observed that, in contrast to EWS cells, MSC were not sensitive to the inhibition of CD99.<h4>Conclusions</h4>In conclusion, our results suggest that MSC from EWS patients behave like MSC-HD and are phenotypically different from EWS cells, thus raising important questions regarding MSC role in sarcomagenesis.
format	article
author	Ana Teresa Amaral Maria Cristina Manara Dagmar Berghuis José Luis Ordóñez Michele Biscuola Maria Angeles Lopez-García Daniel Osuna Enrico Lucarelli Francesco Alviano Arjan Lankester Katia Scotlandi Enrique de Álava
author_facet	Ana Teresa Amaral Maria Cristina Manara Dagmar Berghuis José Luis Ordóñez Michele Biscuola Maria Angeles Lopez-García Daniel Osuna Enrico Lucarelli Francesco Alviano Arjan Lankester Katia Scotlandi Enrique de Álava
author_sort	Ana Teresa Amaral
title	Characterization of human mesenchymal stem cells from ewing sarcoma patients. Pathogenetic implications.
title_short	Characterization of human mesenchymal stem cells from ewing sarcoma patients. Pathogenetic implications.
title_full	Characterization of human mesenchymal stem cells from ewing sarcoma patients. Pathogenetic implications.
title_fullStr	Characterization of human mesenchymal stem cells from ewing sarcoma patients. Pathogenetic implications.
title_full_unstemmed	Characterization of human mesenchymal stem cells from ewing sarcoma patients. Pathogenetic implications.
title_sort	characterization of human mesenchymal stem cells from ewing sarcoma patients. pathogenetic implications.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/463f0eb937254aa4ba9bedb12bfa41eb
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Characterization of human mesenchymal stem cells from ewing sarcoma patients. Pathogenetic implications.

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