dc.contributor.author | Aguirre, GA | en_US |
dc.contributor.author | Goulart, MR | en_US |
dc.contributor.author | Barts Pancreas Tissue Bank | en_US |
dc.contributor.author | Dalli, J | en_US |
dc.contributor.author | Kocher, HM | en_US |
dc.date.accessioned | 2023-11-23T14:58:11Z | |
dc.date.available | 2023-10-26 | en_US |
dc.date.issued | 2023 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/92211 | |
dc.description.abstract | Activation of pancreatic stellate cells (PSCs) to cancer-associated fibroblasts (CAFs) is responsible for the extensive desmoplastic reaction observed in PDAC stroma: a key driver of pancreatic ductal adenocarcinoma (PDAC) chemoresistance leading to poor prognosis. Specialized pro-resolving mediators (SPMs) are prime modulators of inflammation and its resolution, traditionally thought to be produced by immune cells. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based lipid mediator profiling PSCs as well as primary human CAFs express enzymes and receptors to produce and respond to SPMs. Human PSC/CAF SPM secretion profile can be modulated by rendering these cells activated [transforming growth factor beta (TGF-β)] or quiescent [all-trans retinoic acid (ATRA)]. ATRA-induced nuclear translocation of arachidonate-15-lipoxygenase (ALOX15) was linked to increased production of n-3 docosapentaenoic acid-derived Resolvin D5 (RvD5n-3 DPA), among other SPMs. Inhibition of RvD5n-3 DPA formation increases cancer cell invasion, whereas addback of this molecule reduced activated PSC-mediated cancer cell invasion. We also observed that circulating concentrations of RvD5n-3 DPA levels were decreased in peripheral blood of metastatic PDAC patients when compared with those measured in plasma of non-metastatic PDAC patients. Together, these findings indicate that RvD5n-3 DPA may regulate cancer-stroma cross-talk and invasion. | en_US |
dc.format.extent | 1248547 - ? | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | Front Immunol | en_US |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.subject | ALOX15 | en_US |
dc.subject | CAF subtypes | en_US |
dc.subject | all-trans retinoic acid | en_US |
dc.subject | cancer-associated fibroblast | en_US |
dc.subject | lipid mediator | en_US |
dc.subject | pancreatic ductal adenocarcinoma | en_US |
dc.subject | specialized pro-resolving mediator | en_US |
dc.subject | Humans | en_US |
dc.subject | Arachidonate 15-Lipoxygenase | en_US |
dc.subject | Pancreatic Stellate Cells | en_US |
dc.subject | Chromatography, Liquid | en_US |
dc.subject | Tandem Mass Spectrometry | en_US |
dc.subject | Pancreatic Neoplasms | en_US |
dc.subject | Carcinoma, Pancreatic Ductal | en_US |
dc.subject | Tretinoin | en_US |
dc.subject | Neoplasm Invasiveness | en_US |
dc.title | Arachidonate 15-lipoxygenase-mediated production of Resolvin D5n-3 DPA abrogates pancreatic stellate cell-induced cancer cell invasion. | en_US |
dc.type | Article | |
dc.identifier.doi | 10.3389/fimmu.2023.1248547 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/38035115 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 14 | en_US |
dcterms.dateAccepted | 2023-10-26 | en_US |
qmul.funder | Using Signature Lipid Mediator Profiles for Innovative Approaches to Patient Stratification and Precision Medicine::Barts Charity | en_US |