Mass spectrometry-based proteome profiling of extracellular vesicles and their roles in cancer biology

Abstract

Over the past three decades, extracellular vesicles (EVs) have arisen as important mediators of intercellular communication that are involved in the transmission of biological signals between cells to regulate various biological processes. EVs are largely responsible for intercellular communication through the delivery of bioactive molecules, such as proteins, messenger RNAs (mRNAs), microRNAs (miRNAs), DNAs, lipids, and metabolites. EVs released from cancer cells play a significant role in signal transduction between cancer cells and the surrounding cells, which contributes to the formation of tumors and metastasis in the tumor microenvironment. In addition, EVs released from cancer cells migrate to blood vessels and flow into various biological fluids, including blood and urine. EVs and EV-loaded functional cargoes, including proteins and miRNAs, found in these biological fluids are important biomarkers for cancer diagnosis. Therefore, EV proteomics greatly contributes to the understanding of carcinogenesis and tumor progression and is critical for the development of biomarkers for the early diagnosis of cancer. To explore the potential use of EVs as a gateway to understanding cancer biology and to develop cancer biomarkers, we discuss the mass spectrometric identification and characterization of EV proteins from different cancers. Information provided in this review may help in understanding recent progress regarding EV biology and the potential roles of EVs as new noninvasive biomarkers and therapeutic targets.

Fig. 1

Biogenesis of four major subtypes of extracellular vesicles

Fig. 2

Protein–protein interaction network of differentially expressed extracellular vesicle proteins in cancer cell-derived EVs