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Phenotypic, Genomic and Functional Characterization Reveals No Differences between CD138(++) and CD138(low) 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: Paíno, Teresa, Sarasquete, María E., Paiva, Bruno, Krzeminski, Patryk, San-Segundo, Laura, Corchete, Luis A., Redondo, Alba, Garayoa, Mercedes, García-Sanz, Ramón, Gutiérrez, Norma C., Ocio, Enrique M., San-Miguel, Jesús F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962421/
https://www.ncbi.nlm.nih.gov/pubmed/24658332
http://dx.doi.org/10.1371/journal.pone.0092378
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author Paíno, Teresa
Sarasquete, María E.
Paiva, Bruno
Krzeminski, Patryk
San-Segundo, Laura
Corchete, Luis A.
Redondo, Alba
Garayoa, Mercedes
García-Sanz, Ramón
Gutiérrez, Norma C.
Ocio, Enrique M.
San-Miguel, Jesús F.
author_facet Paíno, Teresa
Sarasquete, María E.
Paiva, Bruno
Krzeminski, Patryk
San-Segundo, Laura
Corchete, Luis A.
Redondo, Alba
Garayoa, Mercedes
García-Sanz, Ramón
Gutiérrez, Norma C.
Ocio, Enrique M.
San-Miguel, Jesús F.
author_sort Paíno, Teresa
collection PubMed
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 CD138(low) (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 CD138(low) 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 CD138(low) subpopulations have similar sensitivity to bortezomib, melphalan and doxorubicin. Finally, serial engraftment in CB17-SCID mice shows that CD138(++) as well as CD138(low) 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.
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spelling pubmed-39624212014-03-24 Phenotypic, Genomic and Functional Characterization Reveals No Differences between CD138(++) and CD138(low) Subpopulations in Multiple Myeloma Cell Lines Paíno, Teresa Sarasquete, María E. Paiva, Bruno Krzeminski, Patryk San-Segundo, Laura Corchete, Luis A. Redondo, Alba Garayoa, Mercedes García-Sanz, Ramón Gutiérrez, Norma C. Ocio, Enrique M. San-Miguel, Jesús F. PLoS One Research Article 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 CD138(low) (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 CD138(low) 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 CD138(low) subpopulations have similar sensitivity to bortezomib, melphalan and doxorubicin. Finally, serial engraftment in CB17-SCID mice shows that CD138(++) as well as CD138(low) 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. Public Library of Science 2014-03-21 /pmc/articles/PMC3962421/ /pubmed/24658332 http://dx.doi.org/10.1371/journal.pone.0092378 Text en © 2014 Paíno et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Paíno, Teresa
Sarasquete, María E.
Paiva, Bruno
Krzeminski, Patryk
San-Segundo, Laura
Corchete, Luis A.
Redondo, Alba
Garayoa, Mercedes
García-Sanz, Ramón
Gutiérrez, Norma C.
Ocio, Enrique M.
San-Miguel, Jesús F.
Phenotypic, Genomic and Functional Characterization Reveals No Differences between CD138(++) and CD138(low) Subpopulations in Multiple Myeloma Cell Lines
title Phenotypic, Genomic and Functional Characterization Reveals No Differences between CD138(++) and CD138(low) Subpopulations in Multiple Myeloma Cell Lines
title_full Phenotypic, Genomic and Functional Characterization Reveals No Differences between CD138(++) and CD138(low) Subpopulations in Multiple Myeloma Cell Lines
title_fullStr Phenotypic, Genomic and Functional Characterization Reveals No Differences between CD138(++) and CD138(low) Subpopulations in Multiple Myeloma Cell Lines
title_full_unstemmed Phenotypic, Genomic and Functional Characterization Reveals No Differences between CD138(++) and CD138(low) Subpopulations in Multiple Myeloma Cell Lines
title_short Phenotypic, Genomic and Functional Characterization Reveals No Differences between CD138(++) and CD138(low) Subpopulations in Multiple Myeloma Cell Lines
title_sort phenotypic, genomic and functional characterization reveals no differences between cd138(++) and cd138(low) subpopulations in multiple myeloma cell lines
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962421/
https://www.ncbi.nlm.nih.gov/pubmed/24658332
http://dx.doi.org/10.1371/journal.pone.0092378
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