Under a long-term hypoxia microenvironment, MM cells actively secrete miR-135b–enriched exosomes, which are taken up by the surrounding endothelial cells, leading to reduced expression of FIH-1, one of the miR-135b targets that inhibits the activation of HIF-1. Consequently, the HIF-1 activity is increased in recipient ECs, resulting in an accelerated angiogenesis that may promote MM-cell survival, proliferation, and migration.