BM mesenchymal stromal cell–derived exosomes facilitate multiple myeloma progression
Aldo M. Roccaro, … , David T. Scadden, Irene M. Ghobrial
Aldo M. Roccaro, … , David T. Scadden, Irene M. Ghobrial
Published March 1, 2013
Citation Information: J Clin Invest. 2013;123(4):1542-1555. https://doi.org/10.1172/JCI66517.
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Research Article Oncology

BM mesenchymal stromal cell–derived exosomes facilitate multiple myeloma progression

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.

Authors

Aldo M. Roccaro, Antonio Sacco, Patricia Maiso, Abdel Kareem Azab, Yu-Tzu Tai, Michaela Reagan, Feda Azab, Ludmila M. Flores, Federico Campigotto, Edie Weller, Kenneth C. Anderson, David T. Scadden, Irene M. Ghobrial

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Figure 4

Normal and MM BM-MSC–derived exosomes differentially affect MM cell homing and growth in vivo.

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Normal and MM BM-MSC–derived exosomes differentially affect MM cell homi...
Detection of MM cell homing to the BM was performed by in vivo confocal microscopy (original magnification, ×5). Green, GFP+ MM cells (denoted by arrows); red, Evans Blue–positive blood vessels. Specific BM niches are shown in boxed regions with dotted lines; relative tridimensional reconstruction is shown for each panel (scale expressed in μm). In B, specific BM niches were obtained by changing the focal plane, moving toward the skull of the mouse (boxed region with solid line).