Biological role and clinical relevance of extracellular vesicles as key mediators of cell communication in cancer

Cells of multicellular organisms constantly communicate with each other during development as well as in adult life to regulate body homeostasis and physiology. The sender cells may either signal to themselves or to specific recipient ones, thus influencing many cell processes such as metabolism, division, differentiation and migration. Cell-to-cell communication is extremely relevant in cancer. Tumor cells communicate among them and with several non tumoral cell types, such as stromal, endothelial, immune and epithelial cells, located both in the tumor microenvironment and at distance. The resultant is to sustain or adverse tumor growth and invasion. A great breakthrough in the comprehension of how cells communicate was achieved with the identification of extracellular vesicles (EVs). EVs are lipid membrane encapsulated structures able to transport and deliver in the cells a great variety of molecules, including proteins, metabolites, nucleic acids, lipids and even entire organelles. Most cells, from unicellular prokaryotes to complex multicellular organisms, are able to vesiculate. EVs are very heterogenous in size, content, function and biochemical/biophysical properties. Cancer cells have been shown to release increasing amount of EVs, with a different content respect to normal counterparts and able to elicit several functional responses in target cells. In this chapter we will present the main aspects of EV-based cancer cell communication, highlighting how EVs have been emerging as an extremely powerful tool to better understand tumor biology as well as for clinical applications in neoplastic diseases.