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Published on: December 5, 2025
The ether lipid precursor hexadecylglycerol stimulates the release and changes the composition of exosomes derived
Santosh Phuyal1, Tore Skotland1, Nina Pettersen Hessvik1
1From 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.
Abstract:
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.
