Ludwig Nils, Rubenich Dominique S, Zaręba Łukasz, Siewiera Jacek, Pieper Josquin, Braganhol Elizandra, Reichert Torsten E, Szczepański Mirosław J
Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, 93053 Regensburg, Germany.
Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90050-170, Brazil.
Cancers (Basel). 2020 Dec 2;12(12):3599. doi: 10.3390/cancers12123599.
Extracellular vesicles (EVs) are produced and released by all cells and are present in all body fluids. They exist in a variety of sizes, however, small extracellular vesicles (sEVs), the EV subset with a size range from 30 to 150 nm, are of current interest. They are characterized by a distinct biogenesis and complex cargo composition, which reflects the cytosolic contents and cell-surface molecules of the parent cells. This cargo consists of proteins, nucleic acids, and lipids and is competent in inducing signaling cascades in recipient cells after surface interactions or in initiating the generation of a functional protein by delivering nucleic acids. Based on these characteristics, sEVs are now considered as important mediators of intercellular communication. One hallmark of sEVs is the promotion of angiogenesis. It was shown that sEVs interact with endothelial cells (ECs) and promote an angiogenic phenotype, ultimately leading to increased vascularization of solid tumors and disease progression. It was also shown that sEVs reprogram cells in the tumor microenvironment (TME) and act in a functionally cooperative fashion to promote angiogenesis by a paracrine mechanism involving the differential expression and secretion of angiogenic factors from other cell types. In this review, we will focus on the distinct functions of tumor-cell-derived sEVs (TEX) in promotion of angiogenesis and describe their potential as a therapeutic target for anti-angiogenic therapies. Also, we will focus on non-cancer stroma-cell-derived small extracellular vesicles and their potential role in stimulating a pro-angiogenic TME.
细胞外囊泡（EVs）由所有细胞产生并释放，存在于所有体液中。它们有多种大小，然而，小细胞外囊泡（sEVs），即大小范围在30至150纳米的细胞外囊泡亚群，是当前研究的热点。它们具有独特的生物发生过程和复杂的货物组成，这反映了亲代细胞的胞质内容物和细胞表面分子。这种货物由蛋白质、核酸和脂质组成，能够在表面相互作用后诱导受体细胞中的信号级联反应，或通过传递核酸启动功能性蛋白质的生成。基于这些特性，sEVs现在被认为是细胞间通讯的重要介质。sEVs的一个标志是促进血管生成。研究表明，sEVs与内皮细胞（ECs）相互作用并促进血管生成表型，最终导致实体瘤血管化增加和疾病进展。还表明，sEVs可重编程肿瘤微环境（TME）中的细胞，并以功能协同的方式通过旁分泌机制促进血管生成，该机制涉及其他细胞类型血管生成因子的差异表达和分泌。在本综述中，我们将重点关注肿瘤细胞衍生的sEVs（TEX）在促进血管生成方面的独特功能，并描述它们作为抗血管生成治疗靶点的潜力。此外，我们将重点关注非癌基质细胞衍生的小细胞外囊泡及其在刺激促血管生成TME中的潜在作用。
