Smaller extracellular vesicles are released from pancreatic cancer cells by the alteration of the lipid composition under low glucose conditions
Smaller extracellular vesicles are released from pancreatic cancer cells by the alteration of the lipid composition under low glucose conditions
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在低葡萄糖条件下，通过脂质成分的改变，胰腺癌细胞释放出较小的细胞外囊泡
DOI：
10.1016/j.bbrc.2022.11.040
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发表时间：
2022
影响因子：
3.1
通讯作者：
Fujishiro Mitsuhiro
中科院分区：
文献类型：
--
作者：
Shibata Chikako;Otsuka Motoyuki;Seimiya Takahiro;Ishigaki Kazunaga;Miyakawa Yu;Kishikawa Takahiro;Fujishiro Mitsuhiro
细胞外囊泡（EVs）从细胞释放到血液中，促进细胞间的通讯，并作为新的生物标志物来了解几种疾病的病理生理。尽管对电动汽车内货物的重要性进行了广泛的研究，但对不同类型癌症的电动汽车大小的探索相对较少。在这里，我们发现胰腺癌细胞衍生的电动汽车明显小于非癌细胞衍生的电动汽车。通过特异性分离和检测从胰腺导管腺癌患者血清中分离的异质EV群体中肿瘤来源的EV，证实了这些EV的较小尺寸分布。模拟肿瘤微环境条件的体外分析显示，低糖条件降低了肿瘤源性ev的大小分布，增加了不饱和脂肪酸的水平。由于脂质组成决定了膜的流动性，因此研究结果表明，电动汽车尺寸的改变可能是由于覆盖电动汽车的膜的流动性和稳定性的改变。此外，受体细胞对较小ev的摄取增加，这可能导致功能结果增强。这些结果为确定ev大小的因素提供了基本的见解，这可能对开发癌症筛查方法和了解癌症相关的病理生理学具有重要意义。
Extracellular vesicles (EVs) released from cells into the blood facilitate intercellular communication and serve as new biomarkers to understand the pathophysiology of several conditions. Although the importance of the cargo inside EVs has been extensively studied, the sizes of EVs that vary with different types of cancers are relatively poorly explored. Here, we show that pancreatic cancer cell-derived EVs are significantly smaller than non-cancer cell-derived EVs. The smaller size distribution of these EVs was confirmed by specifically isolating and examining tumor-derived EVs from the heterogeneous EV population isolated from the sera of patients with pancreatic ductal adenocarcinoma. In vitro analyses mimicking tumor microenvironment conditions revealed that low glucose conditions reduced the size distribution and increased the level of unsaturated fatty acids in the tumor-derived EVs. Because the lipid composition defines the fluidity of the membrane, the results suggest that the alterations in the size of EVs could be due to the alteration of the fluidity and stability of the membrane covering the EVs. Furthermore, the uptake of smaller EVs by recipient cells was increased, which may lead to enhanced functional results. These results provide fundamental insights into the factors defining the size of EVs, which may be important for developing cancer screening methods and understanding cancer-related pathophysiology.