Omega-3 polyunsaturated fatty acids regulate syndecan-1 expression in human breast cancer cells.
Human epidemiologic studies and animal model studies support a role for n-3 polyunsaturated fatty acids (n-3 PUFA) in prevention or inhibition of breast cancer. However, mechanisms for this protection remain unclear. Syndecan-1 is a heparan sulfate proteoglycan, expressed on the surface of mammary epithelial cells and known to regulate many biological processes, including cytoskeletal organization, growth factor signaling, and cell-cell adhesion. We studied effects of n-3 PUFA on syndecan-1 expression in human mammary cell lines. PUFA were delivered to cells by low-density lipoproteins (LDL) isolated from the plasma of monkeys fed diets enriched in fish oil (n-3 PUFA) or linoleic acid (n-6 PUFA). Proteoglycan synthesis was measured by incorporation of [35S]-sodium sulfate. No effect of either LDL was observed in nontumorigenic MCF-10A cells, whereas in MCF-7 breast cancer cells, treatment with n-3-enriched LDL but not n-6-enriched LDL resulted in significantly greater synthesis of a proteoglycan identified by immunoprecipitation as syndecan-1. Using real-time reverse transcription-PCR (RT-PCR), it was shown that n-3-enriched LDL significantly increased the expression of syndecan-1 mRNA in a dose-dependent manner and maximal effective time at 8 hours of treatment. The effect was mimicked by an agonist for peroxisome proliferator-activated receptor gamma (PPARgamma) and eliminated by the presence of PPARgamma antagonist suggesting a role for PPARgamma in syndecan enhancement. Our studies show that n-3 LDL modifies the production of syndecan-1 in human breast cancer cells and suggest that biological processes regulated by syndecan-1 may be modified through LDL delivery of n-3 PUFA.
Sun
Haiguo
H
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Berquin
Isabelle M
IM
Edwards
Iris J
IJ
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D047495:PPAR gamma / Q000502:physiology; D011509:Proteoglycans / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053668:Syndecan-1; D053667:Syndecans
D015525:Fatty Acids, Omega-3; D008077:Lipoproteins, LDL; D008562:Membrane Glycoproteins; D047495:PPAR gamma; D011509:Proteoglycans; D012333:RNA, Messenger; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans