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Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells

(2014) BLOOD. 124(4). p.555-566
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Abstract
The interplay between bone marrow stromal cells (BMSCs) and multiple myeloma (MM) cells performs a crucial role in MM pathogenesis by secreting growth factors, cytokines, and extracellular vesicles. Exosomes are membranous vesicles 40 to 100 nm in diameter constitutively released by almost all cell types, and they mediate local cell-to-cell communication by transferring mRNAs, miRNAs, and proteins. Although BMSC-induced growth and drug resistance of MM cells has been studied, the role of BMSC-derived exosomes in this action remains unclear. Here we investigate the effect of BMSC-derived exosomes on the viability, proliferation, survival, migration, and drug resistance of MM cells, using the murine 5T33MM model and human MM samples. BMSCs and MM cells could mutually exchange exosomes carrying certain cytokines. Both naive and 5T33 BMSC-derived exosomes increased MM cell growth and induced drug resistance to bortezomib. BMSC-derived exosomes also influenced the activation of several survival relevant pathways, including c-Jun N-terminal kinase, p38, p53, and Akt. Exosomes obtained from normal donor and MM patient BMSCs also induced survival and drug resistance of human MM cells. Taken together, our results demonstrate the involvement of exosome-mediated communication in BMSC-induced proliferation, migration, survival, and drug resistance of MM cells.
Keywords
NANOPARTICLE TRACKING ANALYSIS, MESENCHYMAL STEM-CELLS, PROMOTE TUMOR-GROWTH, IN-VIVO, LEUKEMIA-CELLS, ENDOTHELIAL-CELLS, SIGNALING PATHWAY, MEMBRANE-VESICLES, SERUM DEPRIVATION, IMMUNE-RESPONSES

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Chicago
Wang, Jinheng, An Hendrix, Sophie Hernot, Miguel Lemaire, ELKE DE BRUYNE, Els Van Valckenborgh, Tony Lahoutte, Olivier De Wever, Karin Vanderkerken, and Eline Menu. 2014. “Bone Marrow Stromal Cell-derived Exosomes as Communicators in Drug Resistance in Multiple Myeloma Cells.” Blood 124 (4): 555–566.
APA
Wang, Jinheng, Hendrix, A., Hernot, S., Lemaire, M., DE BRUYNE, E., Van Valckenborgh, E., Lahoutte, T., et al. (2014). Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells. BLOOD, 124(4), 555–566.
Vancouver
1.
Wang J, Hendrix A, Hernot S, Lemaire M, DE BRUYNE E, Van Valckenborgh E, et al. Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells. BLOOD. 2014;124(4):555–66.
MLA
Wang, Jinheng, An Hendrix, Sophie Hernot, et al. “Bone Marrow Stromal Cell-derived Exosomes as Communicators in Drug Resistance in Multiple Myeloma Cells.” BLOOD 124.4 (2014): 555–566. Print.
@article{5953663,
  abstract     = {The interplay between bone marrow stromal cells (BMSCs) and multiple myeloma (MM) cells performs a crucial role in MM pathogenesis by secreting growth factors, cytokines, and extracellular vesicles. Exosomes are membranous vesicles 40 to 100 nm in diameter constitutively released by almost all cell types, and they mediate local cell-to-cell communication by transferring mRNAs, miRNAs, and proteins. Although BMSC-induced growth and drug resistance of MM cells has been studied, the role of BMSC-derived exosomes in this action remains unclear. Here we investigate the effect of BMSC-derived exosomes on the viability, proliferation, survival, migration, and drug resistance of MM cells, using the murine 5T33MM model and human MM samples. BMSCs and MM cells could mutually exchange exosomes carrying certain cytokines. Both naive and 5T33 BMSC-derived exosomes increased MM cell growth and induced drug resistance to bortezomib. BMSC-derived exosomes also influenced the activation of several survival relevant pathways, including c-Jun N-terminal kinase, p38, p53, and Akt. Exosomes obtained from normal donor and MM patient BMSCs also induced survival and drug resistance of human MM cells. Taken together, our results demonstrate the involvement of exosome-mediated communication in BMSC-induced proliferation, migration, survival, and drug resistance of MM cells.},
  author       = {Wang, Jinheng and Hendrix, An and Hernot, Sophie and Lemaire, Miguel and De Bruyne, Elke and Van Valckenborgh, Els and Lahoutte, Tony and De Wever, Olivier and Vanderkerken, Karin and Menu, Eline},
  issn         = {0006-4971},
  journal      = {BLOOD},
  language     = {eng},
  number       = {4},
  pages        = {555--566},
  title        = {Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells},
  url          = {http://dx.doi.org/10.1182/blood-2014-03562439},
  volume       = {124},
  year         = {2014},
}

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