Probing the mechanisms of extracellular vesicle biogenesis and function in cancer

Abstract

Tumor cells interact with each other, and their surroundings, using a variety of mechanisms to promote virtually all aspects of cancer progression. One such form of intercellular communication that has been attracting considerable attention from the cancer community and the pharmaceutical industry in recent years involves the ability of cancer cells to generate multiple distinct types of non-classical secretory vesicles, generally referred to as extracellular vesicles (EVs). Microvesicles (MVs) represent one of the major classes of EVs and are formed as a result of the outward budding and fission of the plasma membrane. The other main class of EVs is exosomes, which are generated when multivesicular bodies fuse with the cell surface and release their contents into the extracellular space. Both MVs and exosomes have been shown to contain bioactive cargo, including proteins, metabolites, RNA transcripts, microRNAs, and DNA that can be transferred to other cancer cells and stimulate their growth, survival, and migration. However, cancer cell-derived EVs also play important roles in helping re-shape the tumor microenvironment to support tumor expansion and invasive activity, dampen immune responses, as well as enter the circulation to help promote metastatic spread. Here, we provide an overview of what is currently known regarding how the different classes of EVs are generated and contribute to various cancer cell phenotypes. Moreover, we highlight how some of the unique properties of EVs are being used for the development of novel diagnostic and clinical applications.