Extracellular vesicle transfer of cancer pathogenic components

Abstract

Extracellular vesicles (EV), known as exosomes and microvesicles, serve as versatile intercellular communication vehicles. Increasing evidence has shown that cancer cell-derived EV carry pathogenic components, such as proteins, messenger RNA (mRNA), microRNA (miRNA), DNA, lipids and transcriptional factors, that can mediate paracrine signaling in the tumor microenvironment. These data suggest that EV transfer of cancer pathogenic components enable long-distance crosstalk between cancer cells and distant organs, resulting in the promotion of the initial steps for pre-metastatic niche formation. Understanding the metastatic mechanisms through EV transfer may open up a new avenue for cancer therapeutic strategies. Furthermore, the circulating EV have also been of interest as a source for liquid biopsies. EV in body fluids provide a reliable source of miRNA and proteins for cancer biomarkers. The tumor-specific components in EV effectively provide various messages on the physiological and pathological status of cancer patients. Although many researchers are searching for EV biomarkers using miRNA microarrays and proteome analyses, the detection technology for circulating EV in body fluids has not yet reached the point of clinical application. In this review, we summarize recent findings regarding EV function, specifically in metastasis through the transfer of cancer pathogenic components. Furthermore, we highlight the potential of using circulating EV for cancer diagnosis.

Keywords: Biomarker; exosome; extracellular vesicle; metastasis; microRNA.

Figure 1

Schematic representation of the biogenesis and the roles of cancer cell‐derived extracellular vesicles (EV). Cancer cells secrete EV, such as exosomes and microvesicles. Exosomes (size: 50–150 nm) originate within endosomal multivesicular bodies (MVB) and fuse with the plasma membrane. Early endosomes and MVB communicate with the Golgi apparatus through bidirectional vesicle exchange. The MVB can fuse with the lysosome. Microvesicles (size: 100–1000 nm) are shed directly from the plasma membrane. EV contain transmembrane proteins, lipids and nucleic acids (mRNA and miRNA). Cancer cell‐derived EV can transfer to their microenvironmental cells, such as fibroblasts, immune cells and endothelial cells. They can induce myofibroblast differentiation, immune modulation and angiogenesis in each cell. Conversely, mesenchymal stem cell (MSC)‐derived EV can promote cancer cell dormancy. Cell‐to‐cell communication via EV cargo contributes to cancer progression in the tumor microenvironment.

Figure 2

Extracellular vesicle (EV) transfer of cancer pathogenic components. Cancer cell‐derived EV contribute to cancer development, such as invasion and angiogenesis. Furthermore, they carry pathogenic components, such as miRNA and proteins, which can mediate paracrine signaling in tumor microenvironments. Circulating cancer cell‐derived EV promote the initial steps of pre‐metastatic niche formation. In addition, circulating EV miRNA and proteins have also been of interest as a source for liquid biopsy.