Composition, Biogenesis, and Role of Exosomes in Tumor Development

Abstract

The role of exosomes and their mechanism of action at the tumor site have received increasing attention. These microvesicles are produced by a wide range of cells including mesenchymal stem cells (MSCs) and immune cells. In particular, tumor cells release remarkable amounts of exosomes which spread to distant organs through the blood and enhance the possibility of tumor metastasis. In spite of results on tumor promoting properties, there are reports demonstrating the tumor inhibiting effects of exosomes depending on the type of the tumor and cell source. This review aims to have a comprehensive appraisal on the biogenesis, composition, and isolation of exosomes and then highlights the current knowledge of their role in cancer progression or inhibition by special focusing on MSC's exosomes (MSC-EXOs).

Figure 1

Exosome biogenesis and secretion. First, insertion of the cell membrane leads to the formation of early endosomes, and then, endosomes containing RNA and cytosolic proteins are transformed into MVB structures with dynamic subcellular structures. After that, MVBs can be fused with lysosomes and degraded or secreted by plasma membranes and formed exosomes. Finally, exosomes release their cargo, such as DNA, microRNA, and proteins, into the recipient cell in a variety of ways. MVBs: multivesicular bodies.

Figure 2

An overview of exosome functions. MSC-EXOs and tumor-derived exosomes exert various effects on recipient cell through different target/pathway. The interaction between exosome and other cells of TME may result in proliferation, tumor growth, metastasis, and drug resistance. Arrow in the figure above: stimulator. MSC-EXOs: MSC's exosomes; TME: tumor microenvironment; VEGF: vascular endothelial growth factor; CXCR4: C-X-C chemokine receptor type 4; ERK1/2: extracellular signal-regulated kinases 1/2; MAPK: mitogen-activated protein kinases; AKT: protein kinase B; EMT: epithelial–mesenchymal transition; mir: microRNA; MDR: multidrug resistance protein.