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Angiogenesis and vascular stability in eicosanoids and cancer

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Abstract

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.

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Funding

This work was supported by the Else Kröner-Fresenius-Stiftung (Else Kröner-Fresenius-Graduiertenkolleg) and the Deutsche Forschungsgemeinschaft (SFB 1039/A06 and Exzellenzcluster 147 “Cardio-Pulmonary Systems”).

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  1. Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Theodor-Stern-Kai 7, D-60590, Frankfurt am Main, Germany

    Jiong Hu, Timo Frömel & Ingrid Fleming

  2. German Centre for Cardiovascular Research (DZHK) Partner Site RheinMain, Frankfurt, Germany

    Jiong Hu, Timo Frömel & Ingrid Fleming

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  1. Jiong Hu
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Correspondence to Ingrid Fleming.

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Special issue on Bioactive Lipids, Guest Editor: Dipak Panigrahy

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Hu, J., Frömel, T. & Fleming, I. Angiogenesis and vascular stability in eicosanoids and cancer. Cancer Metastasis Rev 37, 425–438 (2018). https://doi.org/10.1007/s10555-018-9732-2

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