Pathological angiogenesis is necessary for tumor development and metastasis. Tumor-derived extracellular vesicles (EVs) play an important role in mediating the crosstalk between cancer cells and vascular endothelial cells. To date, whether and how microRNAs (miRNAs) encapsulated in tumor-derived EVs affect angiogenesis in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we showed that miR-181b-5p, an angiogenesis-promoting miRNA of ESCC, can be transferred from ESCC cells to vascular endothelial cells via EVs. In addition, ESCC-derived EVs-miR-181b-5p dramatically induced angiogenesis by targeting PTEN and PHLPP2, and thereby facilitated tumor growth and metastasis. Moreover, miR-181b-5p was highly expressed in ESCC tissues and serum EVs. High miR-181b-5p expression level in ESCC patients was well predicted for poor overall survival. Our work suggests that intercellular crosstalk between tumor cells and vascular endothelial cells is mediated by tumor-derived EVs. miR-181b-5p-enriched EVs secreted from ESCC cells are involved in angiogenesis that control metastasis of ESCC, providing a potential diagnostic biomarker or drug target for ESCC patients.

病理性血管生成对于肿瘤的发展和转移是必需的。肿瘤来源的细胞外囊泡（EVs）在介导癌细胞与血管内皮细胞之间的串扰中起重要作用。迄今为止，尚不清楚在肿瘤源性电动汽车中封装的微小RNA（miRNA）是否以及如何影响食管鳞状细胞癌（ESCC）的血管生成。在这里，我们显示了miR-181b-5p（一种促进ESCC血管生成的miRNA）可以通过EV从ESCC细胞转移至血管内皮细胞。此外，ESCC衍生的EVs-miR-181b-5p通过靶向PTEN和PHLPP2显着诱导血管生成，从而促进了肿瘤的生长和转移。此外，miR-181b-5p在ESCC组织和血清EV中高表达。ESCC患者中较高的miR-181b-5p表达水平可预测整体生存不良。我们的工作表明，肿瘤细胞与血管内皮细胞之间的细胞间串扰是由肿瘤来源的电动汽车介导的。从ESCC细胞分泌的富含miR-181b-5p的EV参与了控制ESCC转移的血管生成，为ESCC患者提供了潜在的诊断生物标记物或药物靶标。