| Autor: |
Barbara Oliviero, Michele Dei Cas, Aida Zulueta, Roberta Maiello, Alessandro Villa, Carla Martinelli, Elena Del Favero, Monica Falleni, Linda Montavoci, Stefania Varchetta, Dalila Mele, Matteo Donadon, Cristiana Soldani, Barbara Franceschini, Marcello Maestri, Gaetano Piccolo, Matteo Barabino, Paolo Pietro Bianchi, Jesus M. Banales, Stefania Mantovani, Mario U. Mondelli, Anna Caretti |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Scientific Reports, Vol 13, Iss 1, Pp 1-10 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2045-2322 |
| DOI: |
10.1038/s41598-023-34676-w |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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