Proteomic analysis of exosomes secreted by human mesothelioma cells

Proteomic analysis of exosomes secreted by human mesothelioma cells
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DOI:
10.1016/s0002-9440(10)63739-x
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发表时间:
2004-05-01
影响因子:
6
通讯作者:
Lambrecht, BN
Lambrecht, BN
中科院分区:
医学2区
文献类型:
--
作者:
Hegmans, JPJJ;Bard, MPL;Lambrecht, BN

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外泌体是通过胞吐作用分泌到细胞外区室中的小膜囊泡。肿瘤外泌体可参与将抗原取样至抗原呈递细胞或作为允许肿瘤逃避免疫定向破坏的诱饵。肿瘤细胞分泌的外泌体中存在的蛋白质的定义很差。本研究更详细地描述了间皮瘤细胞来源的外泌体的蛋白质组成。外泌体制备物电泳后,使用基质辅助激光解吸电离飞行时间(MALDI-TOF)来表征蛋白质点。发现MHC I类与热休克蛋白HSC 70和HSP 90一起存在。此外,我们还发现了膜联蛋白和PV-1,它们是参与膜转运和功能的蛋白质。细胞骨架蛋白及其相关蛋白埃兹蛋白,膜突蛋白,辅肌动蛋白-4,桥粒斑蛋白,肌成束蛋白也被检测到。除了分子运动驱动蛋白样蛋白外,还检测到许多酶,揭示了外泌体的细胞质定位。最令人感兴趣的是检测发育内皮基因座-1(DEL-1),其可以作为强血管生成因子并且可以增加肿瘤附近的血管发育。总之,间皮瘤细胞释放表达一组离散蛋白质的外来体,这些蛋白质参与抗原呈递、信号转导、迁移和粘附。外泌体可能在肿瘤细胞与其环境之间的相互作用中起重要作用。
Exosomes are small membrane vesicles secreted into the extracellular compartment by exocytosis. Tumor exosomes may be involved in the sampling of antigens to antigen presenting cells or as decoys allowing the tumor to escape immune-directed destruction. The proteins present in exosomes secreted by tumor cells have been poorly defined. This study describes the protein composition of mesothelioma cell-derived exosomes in more detail. After electrophoresis of exosome preparations, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) was used to characterize the protein spots. MHC class I was found to be present together with the heat shock proteins HSC70 and HSP90. in addition, we found annexins and PV-1, proteins involved in membrane transport and function. Cytoskeleton proteins and their associated proteins ezrin, moesin, actinin-4, desmoplakin, and fascin were also detected. Besides the molecular motor kinesin-like protein, many enzymes were detected revealing the cytoplasmic orientation of exosomes. Most interesting was the detection of developmental endothelial locus-1 (DEL-1), which can act as a strong angiogenic factor and can increase the vascular development in the neighborhood of the tumor. in conclusion, mesothelioma cells release exosomes that express a discrete set of proteins involved in antigen presentation, signal transduction, migration, and adhesion. Exosomes may play an important role in the interaction between tumor cells and their environment.