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An omega-3 polyunsaturated fatty acid derivative, 18-HEPE, protects against CXCR4-associated melanoma metastasis
- Source :
- Carcinogenesis
- Publication Year :
- 2018
- Publisher :
- Oxford University Press (OUP), 2018.
-
Abstract
- Melanoma has a high propensity to metastasize and exhibits a poor response to classical therapies. Dysregulation of the chemokine receptor gene CXCR4 is associated with melanoma progression, and although n-3 polyunsaturated fatty acids (PUFAs) are known to be beneficial for melanoma prevention, the underlying mechanism of this effect is unclear. Here, we used the n-3 fatty acid desaturase (Fat-1) transgenic mouse model of endogenous n-3 PUFA synthesis to investigate the influence of elevated n-3 PUFA levels in a mouse model of metastatic melanoma. We found that relative to wild-type (WT) mice, Fat-1 mice exhibited fewer pulmonary metastatic colonies and improved inflammatory indices, including reduced serum tumor necrosis factor alpha (TNF-α) levels and pulmonary myeloperoxidase activity. Differential PUFA metabolites in serum were considered a key factor to alter cancer cell travelling to lung, and we found that n-6 PUFAs such as arachidonic acid induced CXCR4 protein expression although n-3 PUFAs such as eicosapentaenoic acid (EPA) decreased CXCR4 levels. In addition, serum levels of the bioactive EPA metabolite, 18-HEPE, were elevated in Fat-1 mice relative to WT mice, and 18-HEPE suppressed CXCR4 expression in B16-F0 cells. Moreover, relative to controls, numbers of pulmonary metastatic colonies were reduced in WT mice receiving intravenous injections either of 18-HEPE or 18-HEPE-pretreated melanoma cells. Our results indicate that 18-HEPE is a potential anticancer metabolite that mediates, at least in part, the preventive effect of n-3 PUFA on melanoma metastasis.
- Subjects :
- 0301 basic medicine
Genetically modified mouse
Receptors, CXCR4
Cancer Research
Lung Neoplasms
Melanoma, Experimental
Mice, Transgenic
Chrysenes
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cell Line, Tumor
Fatty Acids, Omega-3
Hydroxyeicosatetraenoic Acids
medicine
Animals
Neoplasm Metastasis
Peroxidase
chemistry.chemical_classification
Arachidonic Acid
biology
Tumor Necrosis Factor-alpha
Melanoma
General Medicine
Cadherins
medicine.disease
Eicosapentaenoic acid
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
Fatty acid desaturase
Eicosapentaenoic Acid
chemistry
030220 oncology & carcinogenesis
Cancer cell
biology.protein
Cancer research
Female
Arachidonic acid
Tumor necrosis factor alpha
Inflammation, Microenvironment and Prevention
Polyunsaturated fatty acid
Subjects
Details
- ISSN :
- 14602180 and 01433334
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Carcinogenesis
- Accession number :
- edsair.doi.dedup.....db6309b2e552cdf9999e8d4d5e8e230d