Translational Biomedicine

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Employment of Exosomes for Liquid Biopsies

Matteo Giulietti, Giulia Occhipinti, Alessandra Righetti, Tatiana Armeni, Giovanni Principato, Francesco Piva

Recently, the interest of research has been attracted by a new form of cell-to-cell communication mediated by cell-secreted vesicles known as exosomes. They range from 40 to 120 nm in size and are involved in normal and tumoral biological processes. Mainly, they mediate the intercellular communications both with the cells in the immediate vicinity of the secreting cells and with very distant cells by bloodstream [1]. This cell-to-cell communication is made possible by the transfer into recipient cells of the elements contained in (proteins, DNA and RNAs) and composing (trans-membrane and membrane anchored proteins, lipids) exosomes. These vesicles can be internalized by several routes, such as clathrin-dependent endocytosis, caveolinmediated uptake, macropinocytosis, phagocytosis, and lipid raftmediated internalization [2]. A growing number of studies have shown that these uptake mechanisms involve specific proteinprotein interactions, in particular among exosomal integrins, tetraspanins, proteoglycans and lectins with proteins, such as receptors, on target cell surface [2]. The pattern of external exosomal proteins constitute a code, still to be decrypted, that defines on which cell a vesicle will blend. However, it is still not known how much this uptake is specific, that is, whether it is at tissue or even at cell level. Maybe this pattern regulates also how wide or narrow the spectrum of exosome spread is [3,4].