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Ceramide present in cholangiocarcinoma-derived extracellular vesicle induces a pro-inflammatory state in monocytes
- Source :
- Scientific Reports, Vol 13, Iss 1, Pp 1-10 (2023)
- Publication Year :
- 2023
- Publisher :
- Nature Portfolio, 2023.
-
Abstract
- Abstract Cholangiocarcinoma (CCA) is a rare cancer characterized by a global increasing incidence. Extracellular vesicles (EV) contribute to many of the hallmarks of cancer through transfer of their cargo molecules. The sphingolipid (SPL) profile of intrahepatic CCA (iCCA)-derived EVs was characterized by liquid chromatography-tandem mass spectrometry analysis. The effect of iCCA-derived EVs as mediators of inflammation was assessed on monocytes by flow cytometry. iCCA-derived EVs showed downregulation of all SPL species. Of note, poorly-differentiated iCCA-derived EVs showed a higher ceramide and dihydroceramide content compared with moderately-differentiated iCCA-derived EVs. Of note, higher dihydroceramide content was associated with vascular invasion. Cancer-derived EVs induced the release of pro-inflammatory cytokines in monocytes. Inhibition of synthesis of ceramide with Myriocin, a specific inhibitor of the serine palmitoyl transferase, reduced the pro-inflammatory activity of iCCA-derived EVs, demonstrating a role for ceramide as mediator of inflammation in iCCA. In conclusion, iCCA-derived EVs may promote iCCA progression by exporting the excess of pro-apoptotic and pro-inflammatory ceramides.
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 13
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Scientific Reports
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.bb75d917f167424e9b8d30fa461784d6
- Document Type :
- article
- Full Text :
- https://doi.org/10.1038/s41598-023-34676-w