Pancreatic ductal adenocarcinoma cell secreted extracellular vesicles containing ceramide-1-phosphate promote pancreatic cancer stem cell motility

dc.contributor.authorKuc, Norbert
dc.contributor.authorDoermann, Allison
dc.contributor.authorShirey, Carolyn
dc.contributor.authorLee, Daniel D.
dc.contributor.authorLowe, Chinn-Woan
dc.contributor.authorAwasthi, Niranjan
dc.contributor.authorSchwarz, Roderich E.
dc.contributor.authorStahelin, Robert V.
dc.contributor.authorSchwarz, Margaret A.
dc.contributor.departmentCellular and Integrative Physiology, School of Medicineen_US
dc.date.accessioned2018-10-19T20:01:42Z
dc.date.available2018-10-19T20:01:42Z
dc.date.issued2018-10
dc.description.abstractThe high mortality rate associated with pancreatic ductal adenocarcinoma (PDAC) is in part due to lack of effective therapy for this highly chemoresistant tumor. Cancer stem cells, a subset of cancer cells responsible for tumor initiation and metastasis, are not targeted by conventional cytotoxic agents, which renders the identification of factors that facilitate cancer stem cell activation useful in defining targetable mechanisms. We determined that bioactive sphingolipid induced migration of pancreatic cancer stem cells (PCSC) and signaling was specific to ceramide-1-phosphate (C1P). Furthermore, PDAC cells were identified as a rich source of C1P. Importantly, PDAC cells express the C1P converting enzyme ceramide kinase (CerK), secrete C1P-containing extracellular vesicles that mediate PCSC migration, and when co-injected with PCSC reduce animal survival in a PDAC peritoneal dissemination model. Our findings suggest that PDAC secrete C1P-containing extracellular vesicles as a means of recruiting PCSC to sustain tumor growth therefore making C1P release a mechanism that could facilitate tumor progression.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationKuc, N., Doermann, A., Shirey, C., Lee, D. D., Lowe, C.-W., Awasthi, N., … Schwarz, M. A. (2018). Pancreatic ductal adenocarcinoma cell secreted extracellular vesicles containing ceramide-1-phosphate promote pancreatic cancer stem cell motility. Biochemical Pharmacology, 156, 458–466. https://doi.org/10.1016/j.bcp.2018.09.017en_US
dc.identifier.urihttps://hdl.handle.net/1805/17620
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.isversionof10.1016/j.bcp.2018.09.017en_US
dc.relation.journalBiochemical Pharmacologyen_US
dc.rightsPublisher Policyen_US
dc.sourceAuthoren_US
dc.subjectsphingolipidsen_US
dc.subjecttumor disseminationen_US
dc.subjectceramidesen_US
dc.titlePancreatic ductal adenocarcinoma cell secreted extracellular vesicles containing ceramide-1-phosphate promote pancreatic cancer stem cell motilityen_US
dc.typeArticleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Kuc_2018_pancreatic.pdf
Size:
1.69 MB
Format:
Adobe Portable Document Format
Description:
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.99 KB
Format:
Item-specific license agreed upon to submission
Description: