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

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 half-way 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.