Phenotypic, genomic and functional characterization reveals no differences between CD138++ and CD138low subpopulations in multiple myeloma cell lines.

Despite recent advances in the treatment of multiple myeloma (MM), it remains an incurable disease potentially due to the presence of resistant myeloma cancer stem cells (MM-CSC). Although the presence of clonogenic cells in MM was described three decades ago, the phenotype of MM-CSC is still contro...

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Autores principales:	Teresa Paíno, María E Sarasquete, Bruno Paiva, Patryk Krzeminski, Laura San-Segundo, Luis A Corchete, Alba Redondo, Mercedes Garayoa, Ramón García-Sanz, Norma C Gutiérrez, Enrique M Ocio, Jesús F San-Miguel
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3ed73b7d077a49e0b8fcf3a00b27cc9c
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spelling	oai:doaj.org-article:3ed73b7d077a49e0b8fcf3a00b27cc9c2021-11-18T08:26:46ZPhenotypic, genomic and functional characterization reveals no differences between CD138++ and CD138low subpopulations in multiple myeloma cell lines.1932-620310.1371/journal.pone.0092378https://doaj.org/article/3ed73b7d077a49e0b8fcf3a00b27cc9c2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24658332/?tool=EBIhttps://doaj.org/toc/1932-6203Despite recent advances in the treatment of multiple myeloma (MM), it remains an incurable disease potentially due to the presence of resistant myeloma cancer stem cells (MM-CSC). Although the presence of clonogenic cells in MM was described three decades ago, the phenotype of MM-CSC is still controversial, especially with respect to the expression of syndecan-1 (CD138). Here, we demonstrate the presence of two subpopulations--CD138++ (95-99%) and CD138low (1-5%)--in eight MM cell lines. To find out possible stem-cell-like features, we have phenotypically, genomic and functionally characterized the two subpopulations. Our results show that the minor CD138low subpopulation is morphologically identical to the CD138++ fraction and does not represent a more immature B-cell compartment (with lack of CD19, CD20 and CD27 expression). Moreover, both subpopulations have similar gene expression and genomic profiles. Importantly, both CD138++ and CD138low subpopulations have similar sensitivity to bortezomib, melphalan and doxorubicin. Finally, serial engraftment in CB17-SCID mice shows that CD138++ as well as CD138low cells have self-renewal potential and they are phenotypically interconvertible. Overall, our results differ from previously published data in MM cell lines which attribute a B-cell phenotype to MM-CSC. Future characterization of clonal plasma cell subpopulations in MM patients' samples will guarantee the discovery of more reliable markers able to discriminate true clonogenic myeloma cells.Teresa PaínoMaría E SarasqueteBruno PaivaPatryk KrzeminskiLaura San-SegundoLuis A CorcheteAlba RedondoMercedes GarayoaRamón García-SanzNorma C GutiérrezEnrique M OcioJesús F San-MiguelPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e92378 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Teresa Paíno María E Sarasquete Bruno Paiva Patryk Krzeminski Laura San-Segundo Luis A Corchete Alba Redondo Mercedes Garayoa Ramón García-Sanz Norma C Gutiérrez Enrique M Ocio Jesús F San-Miguel Phenotypic, genomic and functional characterization reveals no differences between CD138++ and CD138low subpopulations in multiple myeloma cell lines.
description	Despite recent advances in the treatment of multiple myeloma (MM), it remains an incurable disease potentially due to the presence of resistant myeloma cancer stem cells (MM-CSC). Although the presence of clonogenic cells in MM was described three decades ago, the phenotype of MM-CSC is still controversial, especially with respect to the expression of syndecan-1 (CD138). Here, we demonstrate the presence of two subpopulations--CD138++ (95-99%) and CD138low (1-5%)--in eight MM cell lines. To find out possible stem-cell-like features, we have phenotypically, genomic and functionally characterized the two subpopulations. Our results show that the minor CD138low subpopulation is morphologically identical to the CD138++ fraction and does not represent a more immature B-cell compartment (with lack of CD19, CD20 and CD27 expression). Moreover, both subpopulations have similar gene expression and genomic profiles. Importantly, both CD138++ and CD138low subpopulations have similar sensitivity to bortezomib, melphalan and doxorubicin. Finally, serial engraftment in CB17-SCID mice shows that CD138++ as well as CD138low cells have self-renewal potential and they are phenotypically interconvertible. Overall, our results differ from previously published data in MM cell lines which attribute a B-cell phenotype to MM-CSC. Future characterization of clonal plasma cell subpopulations in MM patients' samples will guarantee the discovery of more reliable markers able to discriminate true clonogenic myeloma cells.
format	article
author	Teresa Paíno María E Sarasquete Bruno Paiva Patryk Krzeminski Laura San-Segundo Luis A Corchete Alba Redondo Mercedes Garayoa Ramón García-Sanz Norma C Gutiérrez Enrique M Ocio Jesús F San-Miguel
author_facet	Teresa Paíno María E Sarasquete Bruno Paiva Patryk Krzeminski Laura San-Segundo Luis A Corchete Alba Redondo Mercedes Garayoa Ramón García-Sanz Norma C Gutiérrez Enrique M Ocio Jesús F San-Miguel
author_sort	Teresa Paíno
title	Phenotypic, genomic and functional characterization reveals no differences between CD138++ and CD138low subpopulations in multiple myeloma cell lines.
title_short	Phenotypic, genomic and functional characterization reveals no differences between CD138++ and CD138low subpopulations in multiple myeloma cell lines.
title_full	Phenotypic, genomic and functional characterization reveals no differences between CD138++ and CD138low subpopulations in multiple myeloma cell lines.
title_fullStr	Phenotypic, genomic and functional characterization reveals no differences between CD138++ and CD138low subpopulations in multiple myeloma cell lines.
title_full_unstemmed	Phenotypic, genomic and functional characterization reveals no differences between CD138++ and CD138low subpopulations in multiple myeloma cell lines.
title_sort	phenotypic, genomic and functional characterization reveals no differences between cd138++ and cd138low subpopulations in multiple myeloma cell lines.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/3ed73b7d077a49e0b8fcf3a00b27cc9c
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Phenotypic, genomic and functional characterization reveals no differences between CD138++ and CD138low subpopulations in multiple myeloma cell lines.

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