Ceramide present in cholangiocarcinoma-derived extracellular vesicle induces a pro-inflammatory state in monocytes

Journal article

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

Authors: Oliviero, B; Dei Cas, M; Zulueta, A; Maiello, R; Villa, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Scientific Reports
• Volume: 13
• Issue: 1
• Pages: 7766-7766
• Publication date: 2023-05-12
• DOI: 10.1038/s41598-023-34676-w
• EISSN: 2045-2322
• ISSN: 2045-2322
• Language: English
• Keywords: Biochemistry; Sphingolipid; Cancer research; Ceramide; Cell biology; Immunology; Inflammation; Apoptosis; Proinflammatory cytokine; Flow cytometry; Extracellular vesicle; microRNA; Microvesicles; Chemistry; Downregulation and upregulation; Biology