Glycocalyx Acts as a Central Player in the Development of Tumor Microenvironment by Extracellular Vesicles for Angiogenesis and Metastasis

SIMPLE SUMMARY: The glycocalyx is a fluffy sugar coat covering the surface of all mammalian cells. While glycocalyx at endothelial cells is a barrier to tumor cell adhesion and transmigration, glycocalyx at tumor cells promotes tumor metastasis. Angiogenesis at primary tumors and the growth of tumor cells at metastatic sites are all affected by the tumor microenvironment, including the blood vasculature, extracellular matrix (ECM), and fibroblasts. Extracellular vesicles (EVs) secreted by the tumor cells and tumor-associated endothelial cells are also considered to be the components of the tumor microenvironment. They can modify tumor vasculature, ECM, and fibroblasts. But how the EVs are generated, secreted, and up taken by the endothelial and tumor cells in the development of the tumor microenvironment are unclear, especially after anti-angiogenic therapy (AAT). The objective of this short review is to summarize the role of the glycocalyx in EV biogenesis, secretion, and uptake, as well as the modulation of the glycocalyx by the EVs. ABSTRACT: Angiogenesis in tumor growth and progression involves a series of complex changes in the tumor microenvironment. Extracellular vesicles (EVs) are important components of the tumor microenvironment, which can be classified as exosomes, apoptotic vesicles, and matrix vesicles according to their origins and properties. The EVs that share many common biological properties are important factors for the microenvironmental modification and play a vital role in tumor growth and progression. For example, vascular endothelial growth factor (VEGF) exosomes, which carry VEGF, participate in the tolerance of anti-angiogenic therapy (AAT). The glycocalyx is a mucopolysaccharide structure consisting of glycoproteins, proteoglycans, and glycosaminoglycans. Both endothelial and tumor cells have glycocalyx at their surfaces. Glycocalyx at both cells mediates the secretion and uptake of EVs. On the other hand, many components carried by EVs can modify the glycocalyx, which finally facilitates the development of the tumor microenvironment. In this short review, we first summarize the role of EVs in the development of the tumor microenvironment. Then we review how the glycocalyx is associated with the tumor microenvironment and how it is modulated by the EVs, and finally, we review the role of the glycocalyx in the synthesis, release, and uptake of EVs that affect tumor microenvironments. This review aims to provide a basis for the mechanistic study of AAT and new clues to address the challenges in AAT tolerance, tumor angiogenesis and metastasis.