The interplay between bone marrow stromal cells (BMSCs) and multiple myeloma (MM) cells plays a crucial role in MM pathogenesis by secreting growth factors, cytokines, and extracellular vesicles. Exosomes are 40-100 nm diameter membranous vesicles constitutively released by almost all cell types and they mediate local cell-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 investigated 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 the MM cell growth and induced drug resistance to bortezomib. BMSC-derived exosomes also influenced the activation of several survival relevant pathways, including JNK, 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 demonstrated the involvement of exosome-mediated communication in BMSC-induced proliferation, migration, survival, and drug resistance of MM cells.
Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells
Wang J, Hendrix A, Hernot S, Lemaire M, De Bruyne E, Van Valckenborgh E, Lahoutte T, De Wever O, Vanderkerken K, Menu E. (2014) Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells. Blood [Epub ahead of print]. [abstract]