Extracellular Vesicles Are Key Regulators of Tumor Neovasculature.

Naoya Kuriyama,Nobuyoshi Azuma,Shinsuke Kikuchi,Yusuke Yoshioka,Takahiro Ochiya

doi:10.3389/fcell.2020.611039

Abstract

Tumor progression involves a series of biologically important steps in which the crosstalk between cancer cells and the surrounding environment is an important issue. Angiogenesis is a key tumorigenic phenomenon for cancer progression. Tumor-related extracellular vesicles (EVs) modulate the tumor microenvironment (TME) through cell-to-cell communication. Tumor cells in a hypoxic TME release more EVs than cells in a normoxic environment due to uncontrollable tumor proliferation. Tumor-derived EVs in the TME influence endothelial cells (ECs), which then play multiple roles, contributing to tumor angiogenesis, loss of the endothelial vascular barrier by binding to ECs, and subsequent endothelial-to-mesenchymal transition. In contrast, they also indirectly induce tumor angiogenesis through the phenotype switching of various cells into cancer-associated fibroblasts, the activation of tumor-associated ECs and platelets, and remodeling of the extracellular matrix. Here, we review current knowledge regarding the involvement of EVs in tumor vascular-related cancer progression.

Highlights

Extracellular vesicles (EVs) were first discovered in 1967 and initially called “platelet dust,” which was defined as subcellular coagulant materials (Wolf, 1967; Cufaro et al, 2019)
According to the International Society for Extracellular Vesicles (ISEV), extracellular vesicles (EVs) are categorized into several subtypes according to their size or biogenesis: exosomes, MVs, and apoptotic bodies (Witwer et al, 2013; Cufaro et al, 2019)
endothelial-mesenchymal transition (EndoMT) promotes the proliferation and migration of endothelial cells (ECs), resulting in tumor angiogenesis. These findings suggest that ECs that undergo the phenotypic switching migrate to distant organs via tumor-derived EVs and induce tumor angiogenesis in the premetastatic niche as well as in the primary tumor

Summary

Introduction

Extracellular vesicles (EVs) were first discovered in 1967 and initially called “platelet dust,” which was defined as subcellular coagulant materials (Wolf, 1967; Cufaro et al, 2019). It has been well established that cancer cell-derived EVs directly transport VEGF or upregulate the VEGF pathway in ECs, resulting in tumor angiogenesis.

Results

Conclusion