Extracellular vesicles (EVs) from cancer are delivered both proximal and distal organs. EVs are highly glycosylated at the surface where EVs interact with cells and therefore has an impact on their properties and biological functions. Aberrant glycosylation in cancer is associated with cancer progression and metastasis. However, the biological function of glycosylation on the surface of EV is uncovered. We first demonstrated differential glycosylation profiles of EVs and their originated cells, and distinct glycosylation profiles in a brain-metastatic subline BMD2a from its parental human breast cancer cell line, MDA-MB-231-luc-D3H2LN by lectin blot. We then investigated the roles of surface glycoconjugates on EV uptake. N- and/or O-glycosylation removal of fluorescent-labelled BMD2a EVs enhanced cellular uptake to endothelial cells, suggesting that surface glycosylation has inhibitory effects on cellular uptake. Biodistribution of glycosylation-deprived BMD2a EVs administrated intravenously into mice was further analysed ex vivo using near-infrared lipophilic dye. EVs treated with O-deglycosylation enzymes enhanced the accumulation of EVs to the lungs after 24 h from the injection, while N-deglycosylation did not markedly alter biodistribution. As the lungs are first organs in which intravenous blood flows, we suggest that surface glycosylation of cancer-derived EVs avoid promiscuous adhesion to proximal tissues to be delivered to distant organs.

中文翻译：

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通过增强的细胞摄取改变了去糖基化的细胞外囊泡的生物分布。

来自癌症的细胞外囊泡（EV）传递到近端和远端器官。EV在与细胞相互作用的表面高度糖基化，因此对其特性和生物学功能有影响。癌症中异常糖基化与癌症进展和转移有关。然而，未发现EV表面糖基化的生物学功能。我们首先通过凝集素印迹证明了电动汽车及其起源细胞的差异糖基化谱，以及来自其亲本人类乳腺癌细胞系MDA-MB-231-luc-D3H2LN的脑转移亚系BMD2a的脑转移亚谱的独特糖基化谱。然后，我们研究了表面糖缀合物对EV摄取的作用。荧光标记的BMD2a电动汽车的N和/或O-糖基化去除作用增强了细胞对内皮细胞的摄取，提示表面糖基化对细胞摄取具有抑制作用。使用近红外亲脂性染料离体进一步分析了静脉内施用给小鼠的糖基化剥夺的BMD2a EV的生物分布。注射24小时后，用O-去糖基化酶处理的EV增强了EV向肺的积累，而N-去糖基化并没有明显改变生物分布。由于肺是静脉内血液流动的第一器官，因此我们建议，癌症衍生电动车的表面糖基化可避免与近端组织的混杂粘附，从而将其传递到远处的器官。注射24小时后，用O-去糖基化酶处理的EV增强了EV向肺的积累，而N-去糖基化并没有明显改变生物分布。由于肺是静脉内血液流动的第一器官，因此我们建议，癌症衍生电动车的表面糖基化可避免与近端组织的混杂粘附，从而将其传递到远处的器官。注射24小时后，经O-去糖基化酶处理的EV增强了EV向肺的积累，而N-去糖基化并未明显改变生物分布。由于肺是静脉内血液流动的第一器官，因此我们建议，癌症衍生电动车的表面糖基化可避免与近端组织的混杂粘附，从而将其传递到远处的器官。