PMID- 34281173
OWN - NLM
STAT- MEDLINE
DCOM- 20210806
LR  - 20210806
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 13
DP  - 2021 Jul 1
TI  - The Consequences of Soluble Epoxide Hydrolase Deletion on Tumorigenesis and 
      Metastasis in a Mouse Model of Breast Cancer.
LID - 10.3390/ijms22137120 [doi]
LID - 7120
AB  - 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.
FAU - Kesavan, Rushendhiran
AU  - Kesavan R
AUID- ORCID: 0000-0002-8540-8093
AD  - Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe 
      University, 60590 Frankfurt, Germany.
FAU - Fromel, Timo
AU  - Fromel T
AD  - Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe 
      University, 60590 Frankfurt, Germany.
FAU - Zukunft, Sven
AU  - Zukunft S
AUID- ORCID: 0000-0002-1811-4562
AD  - Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe 
      University, 60590 Frankfurt, Germany.
FAU - Brune, Bernhard
AU  - Brune B
AUID- ORCID: 0000-0001-8237-2841
AD  - Institute of Biochemistry I, Faculty of Medicine, Goethe University, 60590 
      Frankfurt, Germany.
FAU - Weigert, Andreas
AU  - Weigert A
AUID- ORCID: 0000-0002-7529-1952
AD  - Institute of Biochemistry I, Faculty of Medicine, Goethe University, 60590 
      Frankfurt, Germany.
FAU - Wittig, Ilka
AU  - Wittig I
AD  - Functional Proteomics, Institute of Cardiovascular Physiology, Faculty of 
      Medicine, Goethe University, 60590 Frankfurt, Germany.
AD  - German Centre for Cardiovascular Research (DZHK) Partner Site RheinMain, 60590 
      Frankfurt, Germany.
FAU - Popp, Rudiger
AU  - Popp R
AD  - Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe 
      University, 60590 Frankfurt, Germany.
FAU - Fleming, Ingrid
AU  - Fleming I
AUID- ORCID: 0000-0003-1881-3635
AD  - Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe 
      University, 60590 Frankfurt, Germany.
AD  - German Centre for Cardiovascular Research (DZHK) Partner Site RheinMain, 60590 
      Frankfurt, Germany.
LA  - eng
GR  - SFB 815/3 Z1/Deutsche Forschungsgemeinschaft/
GR  - EXC 2026, The Cardio-Pulmonary Institute, Project ID: 390649896/Deutsche 
      Forschungsgemeinschaft/
GR  - SFB 1039/2 A06/Deutsche Forschungsgemeinschaft/
GR  - Else Kroner-Fresenius-Graduiertenkolleg/Else Kroner-Fresenius-Stiftung/
PT  - Journal Article
DEP - 20210701
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Epoxy Compounds)
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - EC 3.3.2.10 (Ephx2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/blood supply/genetics/*metabolism/pathology
MH  - Carcinogenesis
MH  - Cell Proliferation/physiology
MH  - Cell Transformation, Neoplastic
MH  - Cytochrome P-450 Enzyme System/metabolism
MH  - Disease Models, Animal
MH  - Epoxide Hydrolases/genetics/*metabolism
MH  - Epoxy Compounds/metabolism
MH  - Fatty Acids, Unsaturated/metabolism
MH  - Female
MH  - Gene Deletion
MH  - Mice
MH  - Mice, Knockout
MH  - Neoplasm Metastasis
MH  - Neovascularization, Pathologic/genetics/metabolism
PMC - PMC8269362
OTO - NOTNLM
OT  - angiogenesis
OT  - cancer metastases
OT  - polyunsaturated fatty acid
COIS- The authors declare no conflict of interest.
EDAT- 2021/07/21 06:00
MHDA- 2021/08/07 06:00
PMCR- 2021/07/01
CRDT- 2021/07/20 01:03
PHST- 2021/06/07 00:00 [received]
PHST- 2021/06/25 00:00 [revised]
PHST- 2021/06/29 00:00 [accepted]
PHST- 2021/07/20 01:03 [entrez]
PHST- 2021/07/21 06:00 [pubmed]
PHST- 2021/08/07 06:00 [medline]
PHST- 2021/07/01 00:00 [pmc-release]
AID - ijms22137120 [pii]
AID - ijms-22-07120 [pii]
AID - 10.3390/ijms22137120 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Jul 1;22(13):7120. doi: 10.3390/ijms22137120.