ArticlePloS one2013
Eicosanoid profiling in an orthotopic model of lung cancer progression by mass spectrometry demonstrates selective production of leukotrienes by inflammatory cells of the microenvironment.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 58 citations in OpenAlex.
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- STAT1/3/5 Functions Driving Lipid and Energy Metabolism in Cancer and Immunity.International journal of molecular sciences · 2026Review
- Decoding the metabolic dialogue in the tumor microenvironment: from immune suppression to precision cancer therapies.Experimental hematology & oncology · 2025Review
- Alpha-Lipoic Acid-Mediated Inhibition of LTBCurrent therapeutic research, clinical and experimental · 2025Article
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- The crosstalk between ferroptosis and anti-tumor immunity in the tumor microenvironment: molecular mechanisms and therapeutic controversy.Cancer communications (London, England) · 2023Review
- GPR183 antagonism reduces macrophage infiltration in influenza and SARS-CoV-2 infection.The European respiratory journal · 2023Article
- Implication of metabolism in the polarization of tumor-associated-macrophages: the mass spectrometry-based point of view.Frontiers in immunology · 2023Review
- Resolvin E1 Reduces Tumor Growth in a Xenograft Model of Lung Cancer.The American journal of pathology · 2022Article
- Signatures of Co-Deregulated Genes and Their Transcriptional Regulators in Lung Cancer.International journal of molecular sciences · 2022Article
- Lipids in cancer: a global view of the contribution of lipid pathways to metastatic formation and treatment resistance.Oncogenesis · 2022Review
- Cysteinyl Leukotriene Pathway and Cancer.International journal of molecular sciences · 2021Review
- Molecular Mechanisms and Cellular Contribution from Lung Fibrosis to Lung Cancer Development.International journal of molecular sciences · 2021Review
- Phospholipase Signaling in Breast Cancer.Advances in experimental medicine and biology · 2021Review
- Lipid Metabolism in Tumor-Associated Macrophages.Advances in experimental medicine and biology · 2021Review
- Communication between human macrophages and epithelial cancer cell lines dictates lipid mediator biosynthesis.Cellular and molecular life sciences : CMLS · 2020Article
- Altered lung tissue lipidomic profile in caspase-4 positive non-small cell lung cancer (NSCLC) patients.Oncotarget · 2020Article
- Metabolic programming of tumor associated macrophages in the context of cancer treatment.Annals of translational medicine · 2020Review
- Eicosanoids in Cancer: New Roles in Immunoregulation.Frontiers in pharmacology · 2020Review
- Activation of PPARγ in Myeloid Cells Promotes Progression of Epithelial Lung Tumors through TGFβ1.Molecular cancer research : MCR · 2019Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Eicosanoids are bioactive lipid mediators derived from arachidonic acid(1) (AA), which is released by cytosolic phospholipase A2 (cPLA2). AA is metabolized through three major pathways, cyclooxygenase (COX), lipoxygenase (LO) and cytochrome P450, to produce a family of eicosanoids, which individually have been shown to have pro- or anti-tumorigenic activities in cancer. However, cancer progression likely depends on complex changes in multiple eicosanoids produced by cancer cells and by tumor microenvironment and a systematic examination of the spectrum of eicosanoids in cancer has not been performed. We used liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) to quantitate eicosanoids produced during lung tumor progression in an orthotopic immunocompetent mouse model of lung cancer, in which Lewis lung carcinoma (LLC) cells are injected into lungs of syngeneic mice. The presence of tumor increased products of both the cyclooxygenase and the lipoxygenase pathways in a time-dependent fashion. Comparing tumors grown in cPLA2 knockout vs wild-type mice, we demonstrated that prostaglandins (PGE2, PGD2 and PGF2a) were produced by both cancer cells and the tumor microenvironment (TME), but leukotriene (LTB4, LTC4, LTD4, LTE4) production required cPLA2 expression in the TME. Using flow cytometry, we recovered tumor-associated neutrophils and 2 types of tumor-associated macrophages from tumor-bearing lungs and we defined their distinct eicosanoid profiles by LC/MS/MS. The combination of flow cytometry and LC/MS/MS unravels the complexity of eicosanoid production in lung cancer and provides a rationale to develop therapeutic strategies that target select cell populations to inhibit specific classes of eicosanoids.
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