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PLoS One. 2014 Mar 21;9(3):e92378. doi: 10.1371/journal.pone.0092378. eCollection 2014.

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

Author information

  • 1Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer/Consejo Superior de Investigaciones Científicas-Universidad de Salamanca, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
  • 2Hospital Universitario de Salamanca, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
  • 3Clínica Universidad de Navarra; Centro de Investigaciones Médicas Aplicadas (CIMA), Pamplona, Spain.
  • 4Hospital Universitario de Salamanca, Salamanca, Spain.
  • 5Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer/Consejo Superior de Investigaciones Científicas-Universidad de Salamanca, Salamanca, Spain; Hospital Universitario de Salamanca, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.

Abstract

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.

PMID:
24658332
[PubMed - indexed for MEDLINE]
PMCID:
PMC3962421
Free PMC Article
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