**4. Extracellular vesicles in cancer metastasis**

The release and (de)regulation of cancer EVs and their cargo critically influence the crosstalk between tumor and stromal in the tumor microenvironment, adjacent normal cells and even distant (pre-) metastatic areas. Various stages of cancer metastasis especially the epithelial-mesenchymal transition (EMT) stage are influenced by cancer stromal cell derived EVs [91]. Mesenchymal stromal cells (MSC) are very important in the cancer stromal EMT induction [92]. There is ample evidence to show that certain components of the cargo carried by MSC-derived EVs could promote cancer metastasis by stimulating, inducing and promoting EMT. Specifically, it was shown that in breast cancer cells, EVs generated from adiposetissue MSCs could activate the Wnt signaling pathway thus promoting cancer cell migration [93]. Again it has been demonstrated that EVs generated from human umbilical cord MSCs promoted EMT through Extracellular signal-regulated kinase (1/2) (ERK) signaling pathway with subsequent promotion of invasion and migration of breast cancer cells [94]. Also in lung cancer, EVs derived human umbilical cord MSCs promoted EMT and when TGF-β in the MSCs were knocked down EMT was inhibited [95].
