Dark-Side of Exosomes.

Exosomes are nanoscale extracellular vesicles that can transport cargos of proteins, lipids, DNA, various RNA species and microRNAs (miRNAs). Exosomes can enter cells and deliver their contents to recipient cell. Owing to their cargo exosomes can transfer different molecules to the target cells and change the phenotype of these cells. The fate of the contents of an exosome depends on its target destination. Various mechanisms for exosome uptake by target cells have been proposed, but the mechanisms responsible for exosomes internalization into cells are still debated. Exosomes exposed cells produce labeled protein kinases, which are expressed by other cells. This means that these kinases are internalized by exosomes, and transported into the cytoplasm of recipient cells. Many studies have confirmed that exosomes are not only secreted by living cells, but also internalized or accumulated by the other cells. The "next cell hypothesis" supports the notion that exosomes constitute communication vehicles between neighboring cells. By this mechanism, exosomes participate in the development of diabetes and its associated complications, critically contribute to the spreading of neuronal damage in Alzheimer's disease, and non-proteolysed form of Fas ligand (mFasL)-bearing exosomes trigger the apoptosis of T lymphocytes. Furthermore, exosomes derived from human B lymphocytes induce antigen-specific major histocompatibility complex (MHC) class II-restricted T cell responses. Interestingly, exosomes secreted by cancer cells have been demonstrated to express tumor antigens, as well as immune suppressive molecules. This process is defined as "exosome-immune suppression" concept. The interplay via the exchange of exosomes between cancer cells and between cancer cells and the tumor stroma promote the transfer of oncogenes and onco-miRNAs from one cell to other. Circulating exosomes that are released from hypertrophic adipocytes are effective in obesity-related complications. On the other hand, the "inflammasome-induced" exosomes can activate inflammatory responses in recipient cells. In this chapter protein kinases-related checkpoints are emphasized considering the regulation of exosome biogenesis, secretory traffic, and their impacts on cell death, tumor growth, immune system, and obesity.