title: 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: Dana-Farber Cancer Institute, Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors: Aldo M
authors: AM
authors: Roccaro
authors: Antonio
authors: A
authors: Sacco
authors: Patricia
authors: P
authors: Maiso
authors: Abdel Kareem
authors: AK
authors: Azab
authors: Yu-Tzu
authors: YT
authors: Tai
authors: Michaela
authors: M
authors: Reagan
authors: Feda
authors: F
authors: Azab
authors: Ludmila M
authors: LM
authors: Flores
authors: Federico
authors: F
authors: Campigotto
authors: Edie
authors: E
authors: Weller
authors: Kenneth C
authors: KC
authors: Anderson
authors: David T
authors: DT
authors: Scadden
authors: Irene M
authors: IM
authors: Ghobrial
mesh_terms: D000368:Aged; D000818:Animals; D019046:Bone Marrow Neoplasms / Q000378:metabolism / Q000556:secondary*; D002465:Cell Movement; D049109:Cell Proliferation; D017077:Culture Media, Conditioned; D018450:Disease Progression; D055354:Exosomes / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005269:Femur / Q000473:pathology; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D009368:Neoplasm Transplantation; D054457:Tissue Scaffolds; D047368:Tumor Burden; D014407:Tumor Cells, Cultured
chemical_list: D017077:Culture Media, Conditioned; C505361:MIRN15 microRNA, human; D035683:MicroRNAs