Exosomal miR146a from multiple myeloma cells regulates cytokine and chemokine secretion in mesenchymal stromal cells

Kim De Veirman, Jinheng Wang, S. XU, Xavier Leleu, Eddy Himpe, Ken Maes, Elke De Bruyne, Els Van Valckenborgh, Karin Vanderkerken, Eline Menu, Ivan Van Riet

Onderzoeksoutput: Meeting abstract (Journal)

Samenvatting

Mutual communication between multiple myeloma (MM) cells and mesenchymal stromal cells (MSC) plays a pivotal role in supporting MM progression. In MM, MSC exhibit a different genomic profile and dysregulated cytokine secretion compared to normal MSC, however the mechanisms involved in these changes are not fully understood. Here, we examined the miRNA changes in human MSC after culture with conditioned medium of MM cells and found 19 dysregulated miRNAs, including upregulated miR-146a. Moreover, exosomes derived from MM cells contained miR-146a and could be transferred into MSC. After overexpressing miR-146a in MSC, secretion of several cytokines and chemokines including CXCL1, IL6, IL-8, IP-10, MCP-1, and CCL-5, was elevated, resulting in the enhancement of MM cell viability and migration. DAPT, an inhibitor of the endogenous Notch pathway, was able to abrogate the miR-146a-induced increase of cytokines in MSC, suggesting the involvement of the Notch pathway. Taken together, our results demonstrate a positive feedback loop between MM cells and MSC: MM cells promote the increase of miR146a in MSC which leads to more cytokine secretion, which in turn favors MM cell growth and migration.

Originele taal-2English
Pagina's (van-tot)28-28
Aantal pagina's1
TijdschriftBelgian Journal of Hematology
StatusPublished - 2016
Evenement31st General Annual Meeting of the Belgian Hematological Society - Dolce La Hulpe, La Hulpe, Belgium
Duur: 29 jan 201630 jan 2016

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