Figure 2.

Schematic representation EVs-mediated interaction in BM microenvironment. MM cells release EVs that contain oncogenic proteins, cytokines, miRs, and other ncRNAs that support: (i) disease progression and drug resistance supporting fibroblast (FBs) activation, conversion of mesenchymal stromal cells (MSCs) into cancer-associated fibroblasts (CAFs) and IL-6 release by bone marrow stromal cells (BMSCs); (ii) bone resorption by increasing proliferation and function of osteoclasts (OCs) and preventing their apoptosis, and by inhibiting osteoblast differentiation; (iii) angiogenesis through the release of pro-angiogenic cytokines and chemokines, which promote the viability of endothelial cells (ECs) and BMSCs and the release of pro-angiogenic factors; and (iv) immunosuppression, which promotes the expansion of myeloid derived suppressor cells (MDSCs) and the production of the immunosuppressive adenosine (ADO). Finally, EVs from BMSCs, in turn, promote the proliferation and viability of MM cells, thus supporting disease progression and drug resistance.