Eicosanoids in the pancreatic tumor microenvironment – a multicellular, multifaceted progression
Eicosanoids in the pancreatic tumor microenvironment – a multicellular, multifaceted progression
ABSTRACT Eicosanoids, oxidized fatty acids that serve as cell-signaling molecules, have been broadly implicated in tumorigenesis. To identify eicosanoids relevant to pancreatic tumorigenesis, we profiled normal pancreas and pancreatic ductal adenocarcinoma (PDAC) in mouse models and patient samples using mass spectrometry. We interrogated RNA sequencing datasets for eicosanoid synthase or receptor expression. Findings were confirmed by immunostaining. In murine models, we identified elevated levels of PGD2, prostacyclin, and thromboxanes in neoplasia while PGE2, 12-HHTre, HETEs, and HDoHEs are elevated specifically in tumors. Analysis of scRNA-seq datasets suggests that PGE2 and prostacyclins are derived from fibroblasts, PGD2 and thromboxanes from myeloid cells, and PGD2 and 5-HETE from tuft cells. In patient samples, we identified a transition from PGD2 to PGE2-producing enzymes in the epithelium during the transition to PDAC, fibroblast/tumor expression of PTGIS, and myeloid/tumor cell expression of TBXAS1. Altogether, our analyses identify key changes in eicosanoid species during pancreatic tumorigenesis and the cell types responsible for their synthesis.
Jytosana Nidhi、DelGiorno Kathleen E.、Singh Pankaj K.、Tan Marcus C.B.、Wahl Geoffrey M.、Gubbala Vikas B.、Lytle Nikki K.、Han Haiyong、Shi Yu、Hunter Tony、Lin Wei、Zhao Steven、Trinh Vincent Q.、Ma Zhibo、Olive Kenneth P.、Kaech Susan M.、Maurer H. Carlo、Naeem Razia F.
Department of Cell and Developmental Biology, Vanderbilt UniversityDepartment of Cell and Developmental Biology, Vanderbilt University||Vanderbilt Digestive Disease Research Center, Vanderbilt University Medical Center||Vanderbilt Ingram Cancer CenterEppley Institute for Research in Cancer, University of Nebraska Medical CenterDepartment of Surgery, Vanderbilt University Medical Center||Vanderbilt Digestive Disease Research Center, Vanderbilt University Medical Center||Vanderbilt Ingram Cancer CenterGene Expression Laboratory, Salk Institute for Biological StudiesGene Expression Laboratory, Salk Institute for Biological StudiesGene Expression Laboratory, Salk Institute for Biological StudiesMolecular Medicine Division, Translational Genomics Research InstituteMolecular and Cell Biology Laboratory, Salk Institute for Biological StudiesMolecular and Cell Biology Laboratory, Salk Institute for Biological StudiesMolecular Medicine Division, Translational Genomics Research InstituteImmunobiology and Microbial Pathogenesis Laboratory, Salk Institute for Biological StudiesDepartment of Surgery, Vanderbilt University Medical CenterGene Expression Laboratory, Salk Institute for Biological StudiesDepartment of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterImmunobiology and Microbial Pathogenesis Laboratory, Salk Institute for Biological StudiesDepartment of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center||Internal Medicine II, School of Medicine, Technische Universit?t M¨1nchenGene Expression Laboratory, Salk Institute for Biological Studies
肿瘤学基础医学生物科学研究方法、生物科学研究技术
tuft cellsprostaglandinsCOX1COX2PTGESPTGISTBXAS1
Jytosana Nidhi,DelGiorno Kathleen E.,Singh Pankaj K.,Tan Marcus C.B.,Wahl Geoffrey M.,Gubbala Vikas B.,Lytle Nikki K.,Han Haiyong,Shi Yu,Hunter Tony,Lin Wei,Zhao Steven,Trinh Vincent Q.,Ma Zhibo,Olive Kenneth P.,Kaech Susan M.,Maurer H. Carlo,Naeem Razia F..Eicosanoids in the pancreatic tumor microenvironment – a multicellular, multifaceted progression[EB/OL].(2025-03-28)[2025-05-06].https://www.biorxiv.org/content/10.1101/2021.10.27.466097.点此复制
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