Emerging roles of exosomes in cancer invasion and metastasis

Abstract

Recent evidence has indicated that nano-sized vesicles called "exosomes" mediate the interaction between cancer cells and their microenvironment and play a critical role in the development of cancers. Exosomes contain cargo consisting of proteins, lipids, mRNAs, and microRNAs that can be delivered to different types of cells in nascent as well as distant locations. Cancer cell-derived exosomes (CCEs) have been identified in body fluids such as urine, plasma, and saliva from patients with cancer. Although their content depends on tumor type and stage, CCEs merit consideration as prognostic and diagnostic markers, as vehicles for drug delivery, and as potential therapeutic targets because they could transport various oncogenic elements. In this review, we summarize recent advances regarding the role of CCEs in cancer invasion and metastasis, as well as its potential clinical applications.

Fig. 1.. Biogenesis, secretion, and intercellular communication of exosomes. Exosomes are formed as intraluminal vesicles (ILVs). Early endosomes are integrated into multivesicular bodies (MVBs), which are the source of exosomes through endosomal sorting complexes required for transport (ESCRT) machinery, lipids (such as ceramide), and the tetraspanins. During the process of ILV formation, proteins (membrane receptors, cytoplasmic proteins, tetraspanins), lipids (cholesterol, ceramide), and nucleic acids (DNA, mRNA, miRNA) are being incorporated into exosomes. MVBs fuse with lysosomes or with the cellular membrane to release exosomes into the extracellular space. Several Rab small GTPases (Rab 11, Rab 27, and Rab 35) are involved in transporting MVBs to the cell membrane and in exosome secretion. The uptake of exosomes into target cells is mediated by the fusion of exosomes with the cell membrane of target cells, by receptor-ligand interactions, or by endocytosis.