1. BM mesenchymal stromal cell--derived exosomes facilitate multiple myeloma progression.
- Author
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Roccaro, Aldo M., Sacco, Antonio, Maiso, Patricia, Azab, Abdel Kareem, Yu-Tzu Tai, Reagan, Michaela, Azab, Feda, Flores, Ludmila M., Campigotto, Federico, Weller, Edie, Anderson, Kenneth C., Scadden, David T., and Ghobrial, Irene M.
- Subjects
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MESENCHYMAL stem cells , *MULTIPLE myeloma , *CANCER cell growth , *CELL communication , *EXOSOMES , *TUMOR suppressor proteins , *CYTOKINES , *CELL adhesion molecules - Abstract
BM mesenchymal stromal cells (BM-MSCs) support multiple myeloma (MM) cell growth, but little is known about the putative mechanisms by which the BM microenvironment plays an oncogenic role in this disease. Cell-cell communication is mediated by exosomes. In this study, we showed that MM BM-MSCs release exosomes that are transferred to MM cells, thereby resulting in modulation of tumor growth in vivo. Exosomal microRNA (miR) content differed between MM and normal BM-MSCs, with a lower content of the tumor suppressor miR-15a. In addition, MM BM-MSC--derived exosomes had higher levels of oncogenic proteins, cytokines, and adhesion molecules compared with exosomes from the cells of origin. Importantly, whereas MM BM-MSC--derived exosomes promoted MM tumor growth, normal BM-MSC exosomes inhibited the growth of MM cells. In summary, these in vitro and in vivo studies demonstrated that exosome transfer from BM-MSCs to clonal plasma cells represents a previously undescribed and unique mechanism that highlights the contribution of BM-MSCs to MM disease progression. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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