Role of stem cell-derived exosomes in cancer

Abstract

Exosomes are small, extracellular membrane- enclosed vesicles that contain a variety of molecules, including proteins, DNA, mRNA and non-coding RNA; these vesicles have been defined as new tools for intercellular communication between cells. Numerous types of cells, including stem cells, secrete exosomes into the extracellular environment, and are significant communicators in the tumor microenvironment. Stem cells are a unique cell population defined by their ability to indefinitely self-renew, differentiate into a variety of cell lines, and form clonal cell populations. Stem cells also secrete large amounts of exosomes, which have demonstrated great potential in a variety of diseases. Increasing evidence has revealed that the mechanism of interaction between stem cells and human tumor cells involves the exchange of biological material through exosomes. In this review, the latest developments in the role of stem cell-derived exosomes in cancer are highlighted.

Keywords: angiogenesis; biomarker; cancer stem cell; exosomes; extracellular vesicles; mesenchymal stem cell; metastasis; multivesicular bodies; stem cell; therapy; tumor growth.

Figure 1.

Biogenesis, contents, secretion and uptake of exosomes. Exosomes are small extracellular membrane-enclosed vesicles that contain a variety of molecules, including proteins, DNA, mRNA and non-coding RNA. Exosomes are initially formed by endocytosis to produce MVBs, and small membranous vesicles within the MVBs are created to produce exosomes. Exosomes contain RNAs/proteins of interest, including tetraspanins CD9 and CD63, cytosolic protein Rab family protein transmembrane molecules MHC I and MHC II, RNA and microRNAs. ESCRT-dependent and ESCRT-independent signals have been demonstrated to regulate the sorting of exosomes. When MVBs are produced, some of them fuse with the cell membrane and release their vesicles into the extracellular space to produce exosomes. Rab family members and soluble NSF-attachment protein receptor complexes play a key role in the secretion of exosomes. After exosomes are secreted, they may be taken up by target cells via direct fusion with the plasma membrane, a receptor-ligand interaction, or endocytosis by phagocytosis. MVB, multivesicular bodies; CD, cluster of differentiation; MHC, major histocompatibility complex; ESCRT, endosomal sorting complex required for transport; Alix, ALG-2-interacting protein X.

Figure 2.

Proposed model for therapeutic application of exosomes. MSC- and CSC-derived exosomes may be used to mediate anti-proliferative or pro-apoptotic effects of anti-cancer therapy. These exosomes may also serve as effective drug delivery vehicles. MSCs, mesenchymal stroma/stem cells; CSCs, cancer stem cells; miRNA, microRNA.