Journal
PLOS ONE
Volume 9, Issue 3, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0092378
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Funding
- Cooperative Research Thematic Network (RTICs) [RD06/0020/0006]
- Junta de Castilla y Leon. Consejeria de Sanidad [GRS 391/B/09]
- Ministerio de Ciencia e Innovacion [PS09/01897]
- Fundacion Memoria D. Samuel Solorzano Barruso [FS/2-2010]
- Asociacion Espanola Contra el Cancer (AECC) [GCB120981SAN]
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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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