Angiogenesis and vascular stability in eicosanoids and cancer

Angiogenesis and inflammation are hallmarks of cancer. Arachidonic acid and other polyunsaturated fatty acids (PUFAs) are primarily metabolized by three distinct enzymatic systems initiated by cyclooxygenases, lipoxygenases, and cytochrome P450 enzymes (CYP) to generate bioactive eicosanoids, includ...

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Bibliographic Details
Published in:Cancer and metastasis reviews 2018-09, Vol.37 (2-3), p.425-438
Main Authors: Hu, Jiong, Frömel, Timo, Fleming, Ingrid
Format: Article
Language:English
Subjects:
Angiogenesis
Animals
Arachidonic acid
Arachidonic Acid - metabolism
Biomarkers
Biomedical and Life Sciences
Biomedicine
Cancer
Cancer Research
Cell proliferation
Cytochrome P-450
Cytochrome P-450 Enzyme System - metabolism
Cytochrome P450
Eicosanoids
Eicosanoids - metabolism
Endothelial cells
Endothelium
Energy Metabolism
Enzymes
Epoxide hydrolase
Health aspects
Humans
Inflammation
Leukotrienes
Lipid Metabolism
Macrophages - immunology
Macrophages - metabolism
Macrophages - pathology
Metabolites
Neoplasms - etiology
Neoplasms - metabolism
Neoplasms - pathology
Neovascularization, Pathologic - metabolism
Oncology
Physiological aspects
Polyunsaturated fatty acids
Prostaglandins
Signal Transduction
Staphylococcal enterotoxin H
Therapeutic applications
Unsaturated fatty acids
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Summary:Angiogenesis and inflammation are hallmarks of cancer. Arachidonic acid and other polyunsaturated fatty acids (PUFAs) are primarily metabolized by three distinct enzymatic systems initiated by cyclooxygenases, lipoxygenases, and cytochrome P450 enzymes (CYP) to generate bioactive eicosanoids, including prostanoids, leukotrienes, hydroxyeicosatetraenoic acids, and epoxyeicosatrienoic acids. As some of the PUFA metabolites playing essential roles in inflammatory processes, these pathways have been widely studied as therapeutic targets of inflammation. Because of their anti-inflammatory effects, these pathways were also proposed as anti-cancer targets. However, although the eicosanoids were linked to endothelial cell proliferation and angiogenesis almost two decades ago, it is only recently PUFA metabolites, especially those generated by CYP enzymes and the soluble epoxide hydrolase (sEH), have been recognized as important signaling mediators in physiological and pathological angiogenesis. Despite the fact that tumor growth and invasion are heavily dependent on inner-tumor angiogenesis and influenced by vascular stability, the role played by PUFA metabolites in tumor angiogenesis and vessel integrity has been largely overlooked. This review highlights current knowledge on the function of PUFA metabolites generated by the CYP/sEH pathway in angiogenesis and vascular stability as well as their potential involvement in cancer development.
ISSN:0167-7659
1573-7233
DOI:10.1007/s10555-018-9732-2