Plasma exosomes from endometrial cancer patients contain LGALS3BP to promote endometrial cancer progression
Plasma exosomes from endometrial cancer patients contain LGALS3BP to promote endometrial cancer progression
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来自子宫内膜癌患者的血浆外泌体含有 LGALS3BP，可促进子宫内膜癌进展。
DOI：
10.1038/s41388-020-01555-x
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发表时间：
2020-11-18
期刊：
影响因子：
8
通讯作者：
Wan, Xiaoping
中科院分区：
文献类型：
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作者：
Song, Yunfeng;Wang, Mengfei;Wan, Xiaoping
子宫内膜癌（Endometrial cancer，EC）是世界范围内常见的妇科恶性肿瘤。外泌体由活细胞分泌并在各种体液中检测到，可以在器官和区室之间交换信息以影响细胞功能，例如增殖、凋亡、迁移和血管生成。我们假设，血浆外泌体内容物在癌症进展过程中发生改变，并通过将生物分子递送到癌症和血管内皮细胞来促进癌症生长和血管生成。在这项研究中，来自EC患者和年龄匹配的健康人的循环外泌体通过商业试剂盒获得。细胞计数试剂盒-8、Transwell和Matrigel管形成测定显示，来自EC患者的循环外泌体促进EC细胞生长和人脐静脉内皮细胞（HUVEC）血管生成。接下来，蛋白质组学分析和ELISA显示，血浆外泌体凝集素半乳糖苷结合可溶性3结合蛋白（LGALS 3BP）在EC进展过程中增加。此外，为了探索外泌体LGALS 3BP的功能，我们通过在人胚肾293细胞中过表达LGALS 3BP来获得含有高水平LGALS 3BP的外泌体，并且我们证明了高含量的外泌体LGALS 3BP通过在体外和体内激活PI 3 K/AKT/VEGFA信号通路来促进EC细胞增殖和迁移以及HUVEC功能。最后，在人EC组织中观察到高LGALS 3BP表达，这表明预后不良。此外，人EC组织的免疫组化分析显示LGALS 3BP表达与VEGFA表达和血管密度相关。因此，我们提出，血浆中含有LGALS 3BP外泌体有助于EC生长和血管生成过程中EC的进展，这也提供了一个新的视角EC的诊断和预后。
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.