Omega-3 polyunsaturated fatty acids down-modulate CXCR4 expression and function in MDA-MB-231 breast cancer cells.
Mol Cancer Res, 2009/7;7(7):1013-20.
Affiliations
PMID: 19567784DOI: 10.1158/1541-7786.MCR-08-0385
Impact factor: 6.333
Abstract
Metastasis is the leading cause of death from breast cancer. A major factor of metastasis is the migration of cancerous cells to other tissues by way of up-regulated chemokine receptors, such as CXCR4, on the cell surface. Much is known of the beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) on cancer; however, the mechanisms behind these effects are unclear. For this study, we investigated the effects of two n-3 PUFAs, docosahexaenoic acid and eicosapentaenoic acid, on CXCR4 expression and activity in the MDA-MB-231 breast cancer cell line. We compared the n-3 PUFAs with the saturated fatty acid stearic acid as a control. Treatment of the cells with n-3 PUFAs resulted in reduced surface expression of CXCR4, but had no effect on overall CXCR4 expression. Consequently, we found that the fatty acid treatment significantly reduced CXCR4-mediated cell migration. Successful CXCR4-mediated signaling and migration requires the cholesterol-rich membrane microdomains known as lipid rafts. Treatment with n-3 PUFAs disrupted the lipid raft domains in a manner similar to methyl-beta-cyclodextrin and resulted in a partial displacement of CXCR4, suggesting a possible mechanism behind the reduced CXCR4 activity. These results were not observed in cells treated with stearic acid. Together, our data suggest that n-3 PUFAs may have a preventative effect on breast cancer metastasis in vitro. This suggests a previously unreported potential benefit of n-3 PUFAs to patients with metastatic breast cancer. The data presented in this study may also translate to other disorders that involve up-regulated chemokine receptors.
MeSH terms
Breast Neoplasms; Caveolin 1; Cell Line, Tumor; Cell Movement; Chemokine CXCL12; Docosahexaenoic Acids; Eicosapentaenoic Acid; Female; Humans; Immunohistochemistry; Membrane Microdomains; Microscopy, Fluorescence; Neoplasm Metastasis; Receptors, CXCR4; Signal Transduction
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