Abstract

Glycans are major constituents of extracellular vesicles (EVs). Alterations in the glycosylation pathway are a common feature of cancer cells, which gives rise to de novo or increased synthesis of particular glycans. Therefore, glycans and glycoproteins have been widely used in the clinic as both stratification and prognosis cancer biomarkers. Interestingly, several of the known tumor-associated glycans have already been identified in cancer EVs, highlighting EV glycosylation as a potential source of circulating cancer biomarkers. These particles are crucial vehicles of cell–cell communication, being able to transfer molecular information and to modulate the recipient cell behavior. The presence of particular glycoconjugates has been described to be important for EV protein sorting, uptake and organ-tropism. Furthermore, specific EV glycans or glycoproteins have been described to be able to distinguish tumor EVs from benign EVs. In this review, the application of EV glycosylation in the development of novel EV detection and capture methodologies is discussed. In addition, we highlight the potential of EV glycosylation in the clinical setting for both cancer biomarker discovery and EV therapeutic delivery strategies.

Highlights

  • This study suggests that the aberrant expression of fucosylation in prostate cancer cell models leads to a decrease of endosomal sorting proteins in the Extracellular vesicles (EVs), such as the endosomal sorting complex required for transport (ESCRT) and other clathrin-mediated endocytosis components, which results in altered protein cargo profiles in the secreted EVs [162]

  • Some of the aberrant glycosylation signatures acquired during cancer progression have been identified in cancer

  • Different studies already gave insights into the biological roles of altered glycosylation during EV uptake, biodistribution and protein cargo sorting. These biological processes were reported to be relevant in cancer progression [169]

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. EVs can be found in various biological fluids and can be harvested in relatively non-invasive ways These particles are attractive systems for targeted drug delivery approaches and valuable sources of circulating cancer biomarkers. Alterations of the glycosylation pathway are a common feature of malignant cell transformation [2,3,4]. These carbohydrates are capable of modulating several processes during cancer progression, including activation of oncogenic signaling pathways, interference with cell–cell and cell–extracellular matrix (ECM) adhesion and mediate cancer cell metastasis [3,4]. Structural of characterization of glycans remains quite challenging.

The Impact of Glycosylation in Cancer Progression
Receptor Tyrosine Kinase Activation
Cell Adhesion Molecules
Immune Response Regulation
Shortcomings of Glycomic Approaches and Their Application in Extracellular
Cancer Extracellular Vesicles Glycosylation
EV Biodistribution and Uptake
Protein Sorting
Cell Behavior Modulation
EV Glycosylation as Therapeutic Delivery Tools
Cancer Biomarker Discovery
Discussion
Full Text
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