Recent progress in the emerging role of exosome in hepatocellular carcinoma

Abstract

Exosomes are small membrane vesicles 50-150 nm in diameter released by a variety of cells, which contain miRNAs, mRNAs and proteins with the potential to regulate signalling pathways in recipient cells. Exosomes deliver nucleic acids and proteins to participate in orchestrating cell-cell communication and microenvironment modulation. In this review, we summarize recent progress in our understanding of the role of exosomes in hepatocellular carcinoma (HCC). This review focuses on recent studies on HCC exosomes, considering biogenesis, cargo and their effects on the development and progression of HCC, including chemoresistance, epithelial-mesenchymal transition, angiogenesis, metastasis and immune response. Finally, we discuss the clinical application of exosomes as a therapeutic agent for HCC.

Keywords: carcinogenesis; exosomes; hepatocellular carcinoma; tumour microenvironment.

Figure 1

The structure of exosome. (A) Receptors on exosome membrane are different due to the donor cells (eg. EGFR). (B) Adhesion molecular includes integrin α/β and the tetraspanins (CD9, CD63, CD81, CD82). (C) Immunoregulator receptor includes MHCI, MHCII and CD86. (D) Exosomal cargo proteins. (E) Nucleic acids. (F) Lipids

Figure 2

The ESCRT complex promotes the formation of exosomes. A, EXCRT‐0 recognizes ubiquitinated cargo and then initiates the budding of exosomes. B, EXCRT‐0 recruits EXCRT‐I; then, EXCRT‐II is recruited by EXCRT‐I and may contribute to cargo clustering. C, EXCRT‐III degrades EXCRT‐0, EXCRT‐I and EXCRT‐II to promote the exosomes budding. This process is accompanied by the deubiquitinated of cargoes. D, EXCRT‐III is disassembled by Vps‐4, resulting in the exosomes budding

Figure 3

Exosomes are taken up by target cells through three main patterns. (A) Receptor derived exosomes uptake. (B) Membrane fusion. (C) Endocytosis by phagocytosis