Eicosanoids in the Pancreatic Tumor Microenvironment—A Multicellular, Multifaceted Progression
Year: 2022
Type: article
Abstract: 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 PGD 2 , prostacyclin, and thromboxanes in neoplasia while PGE 2 , 12-HHTre, HETEs, and HDoHEs are elevated specifically in tumors. Analysis of scRNA-seq datasets suggests that PGE 2 and prostacyclins are derived from fibroblasts, PGD 2 and thromboxanes from myeloid cells, and PGD 2 and 5-HETE from tuft cells. In patient samples, we identified a transition from PGD 2 to PGE 2 -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.
Source: Gastro Hep Advances
Institutions: Salk Institute for Biological Studies, Vanderbilt University, Vanderbilt University Medical Center, Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center, Technical University of Munich, Translational Genomics Research Institute, University of Nebraska Medical Center, Vanderbilt-Ingram Cancer Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,000
Funders: Lustgarten Foundation, Vanderbilt University, Leona M. and Harry B. Helmsley Charitable Trust, Vanderbilt-Ingram Cancer Center, Cumberland Pharmaceuticals, American Gastroenterological Association, Hope Funds for Cancer Research, Salk Institute for Biological Studies, National Institutes of Health, Fred and Pamela Buffett Cancer Center, Vanderbilt Digestive Diseases Research Center, Vanderbilt University Medical Center, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1002678292, G1138875239, G114280915, G1193215683, G1206027067, G150763035, G156378473, G1618482137, G1709937993, G198914242, G2268269956, G2297205415, G2449875888, G281700398, G2822956262, G2969507348, G3101971246, G3269002440, G3274717920, G3323367120, G3391153693, G344109072, G3607157868, G4640128274, G5526428480, G5750880638, G5876873801, G5963266179, G6253640215, G6318372567, G6569741389, G680976502, Combining single cell approaches and a developmental perspective to discover stem cell control circuits and the cellular and molecular bases of cancer heterogeneity, G7029265662, G725763919, G730616897, Signal Transduction by Tyrosine Phosphorylation, G7407543413, G7455644545, G7642566612, G8141923794, G8198779689, G8953775245, G9000037559, G9000055537, G9000064184, G9000076948, G9000089795, G9000133638, G9000156521, G9000232603, G9000261771, G9000279958, G9000338879, Molecular and Cellular Basis for Digestive Diseases, Buffett Cancer Center Support Grant, Cancer Center Support Grant
OpenAlex ID: W4281785876