Phuyal Santosh, Skotland Tore, Hessvik Nina Pettersen, Simolin Helena, Øverbye Anders, Brech Andreas, Parton Robert G, Ekroos Kim, Sandvig Kirsten, Llorente Alicia
From the Department of Biochemistry, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, 0379 Oslo, Norway, the Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway.
the Zora Biosciences Oy, 02150 Espoo, Finland.
J Biol Chem. 2015 Feb 13;290(7):4225-37. doi: 10.1074/jbc.M114.593962. Epub 2014 Dec 17.
Exosomes are vesicles released by cells after fusion of multivesicular bodies with the plasma membrane. In this study, we have investigated whether ether lipids affect the release of exosomes in PC-3 cells. To increase the cellular levels of ether lipids, the ether lipid precursor hexadecylglycerol was added to cells. Lipidomic analysis showed that this compound was in fact able to double the cellular levels of ether lipids in these cells. Furthermore, increased levels of ether lipids were also found in exosomes released by cells containing high levels of these lipids. Interestingly, as measured by nanoparticle tracking analysis, cells containing high levels of ether lipids released more exosomes than control cells, and these exosomes were similar in size to control exosomes. Moreover, silver staining and Western blot analyses showed that the protein composition of exosomes released in the presence of hexadecylglycerol was changed; the levels of some proteins were increased, and the levels of others were reduced. In conclusion, this study clearly shows that an increase in cellular ether lipids is associated with changes in the release and composition of exosomes.
外泌体是多泡体与质膜融合后细胞释放的囊泡。在本研究中，我们研究了醚脂是否会影响PC-3细胞中外泌体的释放。为了提高细胞中醚脂的水平，将醚脂前体十六烷基甘油添加到细胞中。脂质组学分析表明，该化合物实际上能够使这些细胞中醚脂的细胞水平加倍。此外，在含有高水平这些脂质的细胞释放的外泌体中也发现了醚脂水平的增加。有趣的是，通过纳米颗粒跟踪分析测量，含有高水平醚脂的细胞比对照细胞释放更多的外泌体，并且这些外泌体的大小与对照外泌体相似。此外，银染和蛋白质印迹分析表明，在十六烷基甘油存在下释放的外泌体的蛋白质组成发生了变化；一些蛋白质的水平增加，而另一些蛋白质的水平降低。总之，本研究清楚地表明，细胞醚脂的增加与外泌体释放和组成的变化有关。
