TY  - JOUR
A1  - Kesavan, Rushendhiran
A1  - Frömel, Timo
A1  - Zukunft, Sven
A1  - Brüne, Bernhard
A1  - Weigert, Andreas
A1  - Wittig, Ilka
A1  - Popp, Rüdiger
A1  - Fleming, Ingrid
T1  - The consequences of soluble epoxide hydrolase deletion on tumorigenesis and metastasis in a mouse model of breast cancer
T2  - International journal of molecular sciences
N2  - 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.
KW  - polyunsaturated fatty acid
KW  - cancer metastases
KW  - angiogenesis
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/61756
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-617563
SN  - 1422-0067
VL  - 22
IS  - 13
SP  - 1
EP  - 17
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -