Ra really should enhance stratification of MM individuals and their follow-up and danger of progression [109]. Recently, Laurenzana et al. [110] presented a brand new system for isolating EVs from peripheral blood in a single centrifugation step. They applied this system to characterize EVs from HD and MM sufferers by analyzing the size, concentration, and genetic content of EVs. The authors demonstrated elevated levels of CD38 CD138 EVs inside the sera of MM sufferers. Interestingly, the amount of CD38 CD138 EVs correlates with plasmacytosis and disease stage [110]. All round, these studies highlight the promising function of EVs as novel biomarkers for Cells 2021, ten, x FOR PEER Assessment ten of 17 distinguishing clinical illness phase, monitoring MM progression and patient outcome, and predicting the efficacy of therapeutic approaches. 9. Therapeutic Perspective 9. Therapeutic Point of view Considering the fact that EVsEVs identified to play an an important role in MM progression, severalstudies Considering that are are identified to play crucial role in MM progression, a number of studies havehave focusedinhibiting EVs-mediated crosstalk byby blocking the release and/oruptake focused on on inhibiting EVs-mediated crosstalk blocking the release and/or uptake of EVs EVs to stop their tumor-supportive activity [111] (Figure 3A). of to prevent their tumor-supportive activity [111] (Figure 3A).Figure Figure 3. Schematic representation of therapeutic perspectives: (A) inhibition of EVs release and uptake, (B) EVs asas 3. Schematic representation of EV EV therapeutic perspectives: (A) inhibition of EVs release and uptake, (B) EVs therapeutic tools. For a lot more extra information see the primary text. therapeutic tools. For particulars see the principle text.Thompson et al. [112] demonstrated that that heparanase induces releaseEVsEVs tumor Thompson et al. [112] demonstrated heparanase induces release of of by by tucells mor cells and affects their cargo by growing the levels levels of syndecan-1, VEGF, and impacts their protein protein cargo by growing the of syndecan-1, VEGF, and HGFand HGF [112]. Inhibition of heparanase through SST0001 SST0001 suppresses MM cell [112]. Inhibition of heparanase activity activity through suppresses MM cell growth and angiogenesis [113] (Figure 3A).(Figure 3A). The sphingolipid C6 ceramide affects MM growth and angiogenesis [113] The sphingolipid C6 ceramide impacts MM cell proliferation, apoptosis, and EV release, and increases the levelsincreases the levels of tucell proliferation, apoptosis, and EV release, and of tumor-suppressive miRs, like miR-202, miR-16, like miR-202, miR-16, miR-29b, and miR-15a embedded in mor-suppressive miRs, miR-29b, and miR-15a embedded in MM-EVs [114]. GW4869, a neutral sphingomyelinase that prevents EVs budding in the plasma MM-EVs [114]. GW4869, a neutral sphingomyelinase that prevents EVs budding in the plasma membrane [115], is cytotoxic for various MM cell lines and primary MM cells by binding membrane [115], is cytotoxic for a number of MM Moreover, GW4869 MM cells retard the phosphatidylserine expressed on their surface. cell lines and primary is in a position to by binding phosphatidylserine expressed on their surface. Additionally, GW4869 is capable to retard the growth of MM cells expressing phosphatidylserine in a mouse xenograft model [115]. growth 5TGM1 mice with GW4869 reduces osteolysis mouse xenograft model [115]. Therapy ofof MM cells expressing phosphatidylserine in a by increasing OB activity and Therapy of 5TGM1 mice top to a reduces osteoly.
