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Eicosanoid Profiling in an Orthotopic Model of Lung Cancer Progression by Mass Spectrometry Demonstrates Selective Production of Leukotrienes by Inflammatory Cells of the Microenvironment
Eicosanoids are bioactive lipid mediators derived from arachidonic acid(1) (AA), which is released by cytosolic phospholipase A(2) (cPLA(2)). AA is metabolized through three major pathways, cyclooxygenase (COX), lipoxygenase (LO) and cytochrome P450, to produce a family of eicosanoids, which individ...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823604/ https://www.ncbi.nlm.nih.gov/pubmed/24244531 http://dx.doi.org/10.1371/journal.pone.0079633 |
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author | Poczobutt, Joanna M. Gijon, Miguel Amin, Jay Hanson, Dwight Li, Howard Walker, Deandra Weiser-Evans, Mary Lu, Xian Murphy, Robert C. Nemenoff, Raphael A. |
author_facet | Poczobutt, Joanna M. Gijon, Miguel Amin, Jay Hanson, Dwight Li, Howard Walker, Deandra Weiser-Evans, Mary Lu, Xian Murphy, Robert C. Nemenoff, Raphael A. |
author_sort | Poczobutt, Joanna M. |
collection | PubMed |
description | Eicosanoids are bioactive lipid mediators derived from arachidonic acid(1) (AA), which is released by cytosolic phospholipase A(2) (cPLA(2)). 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 cPLA(2) knockout vs wild-type mice, we demonstrated that prostaglandins (PGE(2), PGD(2) and PGF(2a)) were produced by both cancer cells and the tumor microenvironment (TME), but leukotriene (LTB(4), LTC(4), LTD(4), LTE(4)) production required cPLA(2) 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. |
format | Online Article Text |
id | pubmed-3823604 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38236042013-11-15 Eicosanoid Profiling in an Orthotopic Model of Lung Cancer Progression by Mass Spectrometry Demonstrates Selective Production of Leukotrienes by Inflammatory Cells of the Microenvironment Poczobutt, Joanna M. Gijon, Miguel Amin, Jay Hanson, Dwight Li, Howard Walker, Deandra Weiser-Evans, Mary Lu, Xian Murphy, Robert C. Nemenoff, Raphael A. PLoS One Research Article Eicosanoids are bioactive lipid mediators derived from arachidonic acid(1) (AA), which is released by cytosolic phospholipase A(2) (cPLA(2)). 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 cPLA(2) knockout vs wild-type mice, we demonstrated that prostaglandins (PGE(2), PGD(2) and PGF(2a)) were produced by both cancer cells and the tumor microenvironment (TME), but leukotriene (LTB(4), LTC(4), LTD(4), LTE(4)) production required cPLA(2) 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. Public Library of Science 2013-11-11 /pmc/articles/PMC3823604/ /pubmed/24244531 http://dx.doi.org/10.1371/journal.pone.0079633 Text en © 2013 Poczobutt et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Poczobutt, Joanna M. Gijon, Miguel Amin, Jay Hanson, Dwight Li, Howard Walker, Deandra Weiser-Evans, Mary Lu, Xian Murphy, Robert C. Nemenoff, Raphael A. Eicosanoid Profiling in an Orthotopic Model of Lung Cancer Progression by Mass Spectrometry Demonstrates Selective Production of Leukotrienes by Inflammatory Cells of the Microenvironment |
title | Eicosanoid Profiling in an Orthotopic Model of Lung Cancer Progression by Mass Spectrometry Demonstrates Selective Production of Leukotrienes by Inflammatory Cells of the Microenvironment |
title_full | Eicosanoid Profiling in an Orthotopic Model of Lung Cancer Progression by Mass Spectrometry Demonstrates Selective Production of Leukotrienes by Inflammatory Cells of the Microenvironment |
title_fullStr | Eicosanoid Profiling in an Orthotopic Model of Lung Cancer Progression by Mass Spectrometry Demonstrates Selective Production of Leukotrienes by Inflammatory Cells of the Microenvironment |
title_full_unstemmed | Eicosanoid Profiling in an Orthotopic Model of Lung Cancer Progression by Mass Spectrometry Demonstrates Selective Production of Leukotrienes by Inflammatory Cells of the Microenvironment |
title_short | Eicosanoid Profiling in an Orthotopic Model of Lung Cancer Progression by Mass Spectrometry Demonstrates Selective Production of Leukotrienes by Inflammatory Cells of the Microenvironment |
title_sort | eicosanoid profiling in an orthotopic model of lung cancer progression by mass spectrometry demonstrates selective production of leukotrienes by inflammatory cells of the microenvironment |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823604/ https://www.ncbi.nlm.nih.gov/pubmed/24244531 http://dx.doi.org/10.1371/journal.pone.0079633 |
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