Document Detail


Omega-3 polyunsaturated fatty acids down-modulate CXCR4 expression and function in MDA-MB-231 breast cancer cells.
MedLine Citation:
PMID:  19567784     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jeffrey D Altenburg; Rafat A Siddiqui
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Publication Detail:
Type:  Journal Article     Date:  2009-06-30
Journal Detail:
Title:  Molecular cancer research : MCR     Volume:  7     ISSN:  1557-3125     ISO Abbreviation:  Mol. Cancer Res.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-07-17     Completed Date:  2009-12-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101150042     Medline TA:  Mol Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1013-20     Citation Subset:  IM    
Affiliation:
Cellular Biochemistry Laboratory, Methodist Research Institute, Clarian Health Partners, Indianapolis, IN 46202, USA.
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MeSH Terms
Descriptor/Qualifier:
Breast Neoplasms / drug therapy*,  metabolism*,  pathology
Caveolin 1 / metabolism
Cell Line, Tumor
Cell Movement / drug effects
Chemokine CXCL12 / metabolism
Docosahexaenoic Acids / pharmacology*
Eicosapentaenoic Acid / pharmacology*
Female
Humans
Immunohistochemistry
Membrane Microdomains / drug effects,  metabolism
Microscopy, Fluorescence
Neoplasm Metastasis
Receptors, CXCR4 / biosynthesis*,  metabolism
Signal Transduction / drug effects
Chemical
Reg. No./Substance:
0/CXCL12 protein, human; 0/CXCR4 protein, human; 0/Caveolin 1; 0/Chemokine CXCL12; 0/Receptors, CXCR4; 1553-41-9/Eicosapentaenoic Acid; 25167-62-8/Docosahexaenoic Acids

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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