The “sugar‐coated bullets” of cancer: Tumor‐derived exosome surface glycosylation from basic knowledge to applications

Abstract

Scientific interest in exosomes has exploded in recent decades. In 1990 only three articles were published on exosomes, while over 1,700 have already been published halfway into 2020. 1 While researchers have shown much interest in exosomes since being discovered in 1981, an appreciation of the potential role of glycans in exosome structure and function has emerged only recently. Glycosylation is one of the most common post-translational modification, which functions in many physiological and pathological aspects of cellular function. Many components of exosomes are heavily glycosylated including proteins, lipids, among others. Thus, glycosylation undoubtedly has a great impact on exosome biosynthesis and function. Despite the importance of glycosylation in exosomes and the recent recognition of them as biomarkers for not only malignancies but also other system dysfunction and disease, the characterization of exosome glycans remains understudied. In this review, we discuss glycosylation patterns of exosomes derived from various tissues, their biological features, and potential for various clinical applications. We highlight state-of-the-art knowledge about the fine structure of exosomes, which will allow researchers to reconstruct them by surface modification. These efforts will likely lead to novel disease-related biomarker discovery, purification tagging, and targeted drug transfer for clinical applications in the future.

Roles of pulmonary telocytes in airway epithelia to benefit experimental acute lung injury through production of telocyte-driven mediators and exosomes

“…Exosomes contain mRNA, miRNA, and other non-coding RNA, DNA, proteins, and lipids. Of those, heavily glycosylated proteins of exosomes are also considered one of the main elements responsible for exosome biosynthesis and function (Lin et al, 2020 ). With the development of models for reassessment of exosome composition, the heterogeneity of extracellular vesicles was furthermore understood to discover the compartment and mechanisms in human disease (Jeppesen et al, 2019 ).…”

Vesicular Ganglioside GM1 From Breast Tumor Cells Stimulated Epithelial-to-Mesenchymal Transition of Recipient MCF-10A Cells

“…sEV plays a pivotal regulatory role in cell–cell communication and has been implicated in many physiological processes by exchange of vesicular biomolecules including lipid, glycoconjugates, proteins, and RNAs ( 47 , 48 ). Accumulated studies have documented that sEV was heavily glycosylated, and glycosylation has a great effect on sEV biosynthesis and function ( 49 ). Complex N-glycans were identified as determinants of protein trafficking into sEV ( 50 ), and vesicular glycans were also important for their uptake by recipient cells ( 51 ).…”

Fostering “Education”: Do Extracellular Vesicles Exploit Their Own Delivery Code?

“…The relatively low abundance of certain classes of glycopeptides in EVs compared to whole cells or tissues, requires specific enrichment strategies for the MS-based glycoproteomic assay. Two comprehensive reviews [ 94 , 95 ] describe and comment the most common glycoprotein enrichment techniques, such as lectin arrays and other affinity or interaction methods (HILIC), together with strategies based on recent biological and chemical reagents such as those used in click chemistry.…”