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Review
. 2021 Sep;11(9):2783-2797.
doi: 10.1016/j.apsb.2021.01.001. Epub 2021 Jan 7.

The biology, function, and applications of exosomes in cancer

Jinyi Liu  1   2 , Liwen Ren  1   2 , Sha Li  1   2 , Wan Li  1   2 , Xiangjin Zheng  1   2 , Yihui Yang  1   2 , Weiqi Fu  1   2 , Jie Yi  3 , Jinhua Wang  1   2 , Guanhua Du  1   2
Affiliations
Review

The biology, function, and applications of exosomes in cancer

Jinyi Liu et al. Acta Pharm Sin B. 2021 Sep.

Abstract

Exosomes are cell-derived nanovesicles with diameters from 30 to 150 nm, released upon fusion of multivesicular bodies with the cell surface. They can transport nucleic acids, proteins, and lipids for intercellular communication and activate signaling pathways in target cells. In cancers, exosomes may participate in growth and metastasis of tumors by regulating the immune response, blocking the epithelial-mesenchymal transition, and promoting angiogenesis. They are also involved in the development of resistance to chemotherapeutic drugs. Exosomes in liquid biopsies can be used as non-invasive biomarkers for early detection and diagnosis of cancers. Because of their amphipathic structure, exosomes are natural drug delivery vehicles for cancer therapy.

Keywords: ABCA3, ATP-binding cassette transporter A3; APCs, antigen-presenting cells; Biomarkers; CAFs, cancer-associated fibroblasts; CCRCC, clear-cell renal cell carcinoma; CD-UPRT, cytosine deaminase-uracil phosphoribosyltransferase; CDH3, cadherin 3; CRC, colorectal cancer; DC, dendritic cells; DEXs, DC-derived exosomes; DLBCL, diffuse large B-cell lymphoma; DNM3, dynamin 3; Del-1, developmental endothelial locus-1; Drug delivery; Drug resistance; ECM, extracellular matrix; EMT, epithelial–mesenchymal transition; ESCRT, endosomal sorting complex required for transport; Exosomes; GPC1, glypican-1; HA, hyaluronic acid; HCC, hepatocellular carcinoma; HIF1, hypoxia-inducible factor 1; HTR, hormone therapy-resistant; HUVECs, human umbilical vein endothelial cells; ILVs, intraluminal vesicles; MDSCs, myeloid-derived suppressor cells; MIF, migration inhibitory factor; MSC, mesenchymal stem cells; MVB, multivesicular body; NKEXOs, natural killer cell-derived exosomes; NNs, nanoparticles; NSCLC, non-small cell lung cancer; PA, phosphatidic acid; PCC, pheochromocytoma; PD-L1, programmed cell death receptor ligand 1; PDAC, pancreatic ductal adenocarcinoma; PGL, paraganglioma; PI, phosphatidylinositol; PS, phosphatidylserine; PTRF, polymerase I and transcript release factor; RCC, renal cell carcinoma; SM, sphingomyelin; SNARE, soluble NSF-attachment protein receptor; TEX, tumor-derived exosomes; TSG101, tumor susceptibility gene 101; Tumor immunity; Tumor metastasis; circRNAs, circular RNAs; dsDNA, double stranded DNA; hTERT, human telomerase reverse transcriptase; lamp2b, lysosome-associated membrane glycoprotein 2b; lncRNAs, long non-coding RNAs; miRNA, microRNA; mtDNA, mitochondrial DNA; ncRNA, non-coding RNAs.

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Figures

Image 1
Graphical abstract
Figure 1
Figure 1
Schematic representation of structure of exosomes containing RNA, DNA, protein and metabolites surrounded by lipid bilayer.
Figure 2
Figure 2
Schematic representation of the origin and release of exosomes. Exosomes are formed as ILVs by budding into early endosomes and MVBs. ESCRT, lipids and tetraspanins are involved in the biogenesis of MVBs. MVBs can be either fused with lysosomes or with the plasma membrane, which allows the release of their contents to the extracellular milieu. RAB and SNARE are involved in the transport of MVBs to the plasma membrane and secretion of exosomes.
Figure 3
Figure 3
Schematic representation of exosomes in tumor metastasis and targeted therapy. Exosomes promote epithelial–mesenchymal transition, angiogenesis and extracellular matrix remodeling in the tumor microenvironment. Exosomes can also help tumor cells escape from immune surveillance, promote formation of pre-metastatic niches and allow cancer cells to invade and colonize distant organs. Different types of therapeutic payloads including small molecule drugs, proteins and nucleic acids can be loaded into exosomes, which can then be targeted to tumor tissues.
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