肝星状细胞
癌症研究
癌细胞
胰腺癌
基质
化学
肿瘤微环境
炎症
维甲酸
生物
癌症
医学
内科学
内分泌学
免疫学
生物化学
免疫组织化学
肿瘤细胞
基因
作者
Gabriel A. Aguirre,Michelle R. Goulart,Jesmond Dalli,Hemant M. Kocher
标识
DOI:10.3389/fimmu.2023.1248547
摘要
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 (RvD5 n-3 DPA ), among other SPMs. Inhibition of RvD5 n-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 RvD5 n-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 RvD5 n-3 DPA may regulate cancer–stroma cross-talk and invasion.
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