Plasma exosomes from endometrial cancer patients contain LGALS3BP to promote endometrial cancer progression

血管生成 微泡 生物 癌症研究 癌症 基质凝胶 肿瘤进展 外体 血管内皮生长因子A 细胞生长 血管内皮生长因子 免疫学 癌细胞 小RNA 生物化学 血管内皮生长因子受体 基因 遗传学
作者
Yiran Song,Mengfei Wang,Huan Tong,Yuan Tan,Xiang Hu,Kai Wang,Xiaoping Wan
出处
期刊:Oncogene [Springer Nature]
卷期号:40 (3): 633-646 被引量:55
标识
DOI:10.1038/s41388-020-01555-x
摘要

Endometrial cancer (EC) is a common gynaecological cancer worldwide. Exosomes, secreted by living cells and detected in various body fluids, can exchange information between organs and compartments to affect cellular functions, such as proliferation, apoptosis, migration and angiogenesis. We hypothesise that plasma exosomal contents are altered during cancer progression and promote cancer growth and angiogenesis by delivering biomolecules to cancer and vascular endothelial cells. In this study, circulating exosomes derived from EC patients and age-matched healthy people were acquired by commercial kits. Cell counting kit-8, Transwell and Matrigel tube formation assays showed that circulating exosomes from EC patients promote EC cell growth and human umbilical vein endothelial cell (HUVEC) angiogenesis. Next, proteomic analysis and ELISA revealed that plasma exosomal lectin galactoside-binding soluble 3 binding protein (LGALS3BP) increased during EC progression. Moreover, to explore the function of exosomal LGALS3BP, we acquired exosomes containing high levels of LGALS3BP by overexpressing LGALS3BP in human embryonic kidney 293 cells, and we demonstrated that highly contained exosomal LGALS3BP contributed to EC cell proliferation and migration and HUVEC functions via the activation of the PI3K/AKT/VEGFA signalling pathway both in vitro and in vivo. Finally, high LGALS3BP expression was observed in human EC tissue, which indicated a poor prognosis. In addition, immunohistochemical analysis of human EC tissues revealed that LGALS3BP expression was correlated with VEGFA expression and blood vessel density. Hence, we proposed that plasma exosomes containing LGALS3BP contributed to EC growth and angiogenesis during EC progression, which also provided a novel perspective on EC diagnosis and prognosis.
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