Abstract
Angiogenesis is required for tumor growth and development. Extracellular vesicles (EVs) are important signaling entities that mediate communication between diverse types of cells and regulate various cell biological processes, including angiogenesis. Recently, emerging evidence has suggested that tumor-derived EVs play essential roles in tumor progression by regulating angiogenesis. Thousands of molecules are carried by EVs, and the two major types of biomolecules, noncoding RNAs (ncRNAs) and proteins, are transported between cells and regulate physiological and pathological functions in recipient cells. Understanding the regulation of EVs and their cargoes in tumor angiogenesis has become increasingly important. In this review, we summarize the effects of tumor-derived EVs and their cargoes, especially ncRNAs and proteins, on tumor angiogenesis and their mechanisms, and we highlight the clinical implications of EVs in bodily fluids as biomarkers and as diagnostic, prognostic, and therapeutic targets in cancer patients.
Highlights
Angiogenesis, defined as the establishment of new blood vessels from pre-existing vascular networks, is triggered by proangiogenic factors and depends on the proliferation and migration of endothelial cells (ECs) (Teleanu et al, 2019; Lugano et al, 2020)
MiRNA-derived from tumor-secreted Extracellular vesicles (EVs) regulate angiogenesis primarily by modulating the vascular endothelial growth factor (VEGF)/ VEGFR and HIF-1α signaling pathways. In addition to those derived from tumor cells, EVs derived from cancerassociated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) have been shown to regulate tumor angiogenesis via various mechanisms
Tumor angiogenesis plays a critical role in tumor growth and development, and antiangiogenic therapy has been frequently applied to the clinical treatment of multiple solid tumors
Summary
Angiogenesis, defined as the establishment of new blood vessels from pre-existing vascular networks, is triggered by proangiogenic factors and depends on the proliferation and migration of endothelial cells (ECs) (Teleanu et al, 2019; Lugano et al, 2020). EVs contain many bioactive molecules, such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and proteins, and these EV cargoes regulate intercellular communication (Mathieu et al, 2019; Liu. Extracellular Vesicles and Tumor Angiogenesis et al, 2021). Tumor-derived EVs can transfer proangiogenic molecules into ECs to promote their angiogenic activity via various mechanisms such as VEGF/VEGF Receptor (VEGF/ VEGFR), Notch, Wingless-type (WNT), and Hypoxiainducible factor (HIF) signaling pathway (Phng et al, 2009; Horie et al, 2017; Todorova et al, 2017; Aslan et al, 2019). A database of exosomes (http:// www.exocarta.org/) includes 9,769 proteins, 3,408 mRNAs, and 2,838 miRNAs. The mechanisms triggered by these specific cargos loaded into EVs and delivered from donor cells to acceptor cells are complex (Abels and Breakefield, 2016; Mathieu et al, 2019). We discuss the main prospects for their applications in cancer diagnosis, prognosis, and treatment
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