Abstract

Exosome-mediated Transfer of microRNAs Plays a Crucial Role in Multiple Myeloma Pathogenesis

Aldo Roccaro, Senior Scientist, Dana Farber Cancer Institute

It has been demonstrated that microRNAs (miRNAs) are deregulated in clonal plasma cells of patients with multiple myeloma (MM), thus supporting MM pathogenesis and disease progression. We hypothesized that the surrounding bone marrow (BM) microenvironment may be responsible for mediating changes in miRNA expression in clonal MM cells, through the release of exosomes and their subsequent transfer to MM tumor cells. We demonstrated that BM-derived exosomes are transferred into MM cells together with their miRNA content. This led to modulation of miRNA profiling in MM cells, thus resulting in modulation of MM cell growth and disease dissemination, as demonstrated both in vitro and in vivo. Our findings demonstrate the existence of exosome-driven interactions between the BM milieu and MM cells, suggesting that exosomes constitute a novel mechanism for intercellular transfer of genetic information in the form of miRNAs in MM.