Ceramide present in cholangiocarcinoma-derived extracellular vesicle induces a pro-inflammatory state in monocytes.-Reference-Cited by-同舟云学术

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

Published:2023-01-27 Issue: Volume: Page:
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Author:

Oliviero Barbara¹,Cas Michele Dei²,Zulueta Aida³,Maiello Roberta⁴,Villa Alessandro²,Martinelli Carla²,Favero Elena Del⁵,Falleni Monica⁶,Montavoci Linda²,Varchetta Stefania¹,Mele Dalila¹,Donadon Matteo⁷,Soldani Cristiana⁸,Franceschini Barbara⁸,Maestri Marcello⁹,Piccolo Gaetano¹⁰,Barabino Matteo¹⁰,Bianchi Paolo²,Banales Jesus M¹¹,Mantovani Stefania¹,Mondelli Mario¹²,Caretti Anna²

Affiliation:

1. Department of Medicine, Division of Clinical Immunology - Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia

2. Department of Health Sciences, University of Milan

3. Istituti Clinici Scientifici Maugeri IRCCS, Neurorehabilitation Unit of Milan Institute

4. Department of Molecular Medicine, University of Pavia

5. Department of Medical Biotechnology and Translational Medicine, University of Milan

6. Pathology Division, Health Sciences Department, University of Milan

7. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan

8. Laboratory of Hepatobiliary Immunopathology, IRCCS Humanitas Research Hospital, Rozzano

9. Division of General Surgery 1, Fondazione IRCCS Policlinico San Matteo, Pavia

10. Division of Gastrointestinal Surgery, ASST Santi Paolo e Carlo, and State University of Milan, Milan

11. Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute-Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain; National Instit

12. Department of Internal Medicine and Therapeutics, University of Pavia

Abstract

Abstract Cholangiocarcinoma (CCA) is a rare cancer with 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. Higher ceramide and dihydroceramide content was associated with vascular invasion, larger tumor size and relevant expression 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 capacity of iCCA-derived EVs, demonstrating the role for ceramide as mediator of inflammation in iCCA. In conclusion, iCCA-derived EVs may facilitate iCCA progression by exporting the excess of pro-apoptotic and pro-inflammatory ceramides.

Publisher

Research Square Platform LLC

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