The consequences of soluble epoxide hydrolase deletion on tumorigenesis and metastasis in a mouse model of breast cancer

  • Epoxides and diols of polyunsaturated fatty acids (PUFAs) are bioactive and can influence processes such as tumor cell proliferation and angiogenesis. Studies with inhibitors of the soluble epoxide hydrolase (sEH) in animals overexpressing cytochrome P450 enzymes or following the systemic administration of specific epoxides revealed a markedly increased incidence of tumor metastases. To determine whether PUFA epoxides increased metastases in a model of spontaneous breast cancer, sEH-/- mice were crossed onto the polyoma middle T oncogene (PyMT) background. We found that the deletion of the sEH accelerated the growth of primary tumors and increased both the tumor macrophage count and angiogenesis. There were small differences in the epoxide/diol content of tumors, particularly in epoxyoctadecamonoenic acid versus dihydroxyoctadecenoic acid, and marked changes in the expression of proteins linked with cell proliferation and metabolism. However, there was no consequence of sEH inhibition on the formation of metastases in the lymph node or lung. Taken together, our results confirm previous reports of increased tumor growth in animals lacking sEH but fail to substantiate reports of enhanced lymph node or pulmonary metastases.

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Author:Rushendhiran Kesavan, Timo Frömel, Sven Zukunft, Bernhard BrüneORCiD, Andreas WeigertORCiDGND, Ilka WittigORCiD, Rüdiger Popp, Ingrid FlemingORCiD
Parent Title (English):International journal of molecular sciences
Publisher:Molecular Diversity Preservation International
Place of publication:Basel
Document Type:Article
Date of Publication (online):2021/07/01
Date of first Publication:2021/07/01
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/07/26
Tag:angiogenesis; cancer metastases; polyunsaturated fatty acid
Page Number:17
First Page:1
Last Page:17
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0