MIF and neoplasm: In the past, we also described the relevance of the protein content in tumor EV bioactivity, when we described that once taken up by hepatic resident macrophages, in a mechanism mediated by EV Integrin αVβ5 (Hoshino et al., 2015), pancreatic cancer-derived EVs containing high levels of MIF (Costa-Silva et al., 2015) induced upregulation of secreted factors associated with liver fibrosis, such as TGF-β (Costa-Silva et al., 2015), and pro-inflammatory genes involved with metastasis, such as S100A8 and S100P (Lukanidin and Sleeman, 2012; Hoshino et al., 2015).