학술논문
Ceramide present in cholangiocarcinoma-derived extracellular vesicle induces a pro-inflammatory state in monocytes.
Document Type
Article
Author
Oliviero, Barbara; Dei Cas, Michele; Zulueta, Aida; Maiello, Roberta; Villa, Alessandro; Martinelli, Carla; Del Favero, Elena; Falleni, Monica; Montavoci, Linda; Varchetta, Stefania; Mele, Dalila; Donadon, Matteo; Soldani, Cristiana; Franceschini, Barbara; Maestri, Marcello; Piccolo, Gaetano; Barabino, Matteo; Bianchi, Paolo Pietro; Banales, Jesus M.; Mantovani, Stefania
Source
Subject
*EXTRACELLULAR vesicles
*INFLAMMATION
*CERAMIDES
*MONOCYTES
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Language
ISSN
2045-2322
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. [ABSTRACT FROM AUTHOR]