Document Detail


BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression.
MedLine Citation:
PMID:  23454749     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  123     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-05-09     Completed Date:  2013-05-20     Revised Date:  2013-09-24    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1542-55     Citation Subset:  AIM; IM    
Affiliation:
Dana-Farber Cancer Institute, Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts 02215, USA.
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE39571
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MeSH Terms
Descriptor/Qualifier:
Aged
Animals
Bone Marrow Neoplasms / metabolism,  secondary*
Cell Movement
Cell Proliferation
Culture Media, Conditioned
Disease Progression
Exosomes / metabolism,  physiology*
Female
Femur / pathology
Humans
Mesenchymal Stem Cell Transplantation
Mesenchymal Stromal Cells / metabolism*,  physiology
Mice
Mice, Inbred C57BL
Mice, SCID
MicroRNAs / genetics,  metabolism
Middle Aged
Multiple Myeloma / metabolism,  pathology*
Neoplasm Transplantation
Tissue Scaffolds
Tumor Burden
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
P01 CA078378/CA/NCI NIH HHS; P01 CA155258/CA/NCI NIH HHS; P50 CA100707/CA/NCI NIH HHS; R01 CA050947/CA/NCI NIH HHS; R01 CA154648/CA/NCI NIH HHS; R01CA125690/CA/NCI NIH HHS; R01CA133799/CA/NCI NIH HHS; R01CA154648/CA/NCI NIH HHS; U01 HL100402/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Culture Media, Conditioned; 0/MIRN15 microRNA, human; 0/MicroRNAs
Comments/Corrections
Erratum In:
J Clin Invest. 2013 Aug 1;123(8):3635

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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