Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs.
Epidemiological studies have shown not only a relationship between the intake of dietary lipids and an increased risk of developing metastatic prostate cancer, but also the type of lipid intake that influences the risk of metastatic prostate cancer. The Omega-6 poly-unsaturated fatty acid, Arachidonic acid, has been shown to enhance the proliferation of malignant prostate epithelial cells and increase the risk of advanced prostate cancer. However, its role in potentiating the migration of cancer cells is unknown. Here we show that arachidonic acid at concentrations <or=5 microM is a potent stimulator of malignant epithelial cellular invasion, which is able to restore invasion toward hydrocortisone-deprived adipocyte-free human bone marrow stroma completely. This observed invasion is mediated by the arachidonic acid metabolite prostaglandin E2 and is inhibited by the Omega-3 poly-unsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid at a ratio of 1 : 2 Omega-3 : Omega-6, and by the COX-2 inhibitor NS-398. These results identify a mechanism by which arachidonic acid may potentiate the risk of metastatic migration and secondary implantation in vivo, a risk which can be reduced with the uptake of Omega-3 poly-unsaturated fatty acids.
Brown
M D
MD
ProMPT Genito Urinary Cancer Research Group, Cancer Research UK. mbrown@picr.man.ac.uk
Hart
C A
CA
Gazi
E
E
Bagley
S
S
Clarke
N W
NW
D016718:Arachidonic Acid / Q000494:pharmacology*; D019046:Bone Marrow Neoplasms / Q000556:secondary*; D002465:Cell Movement; D004305:Dose-Response Relationship, Drug; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D012307:Risk Factors; D014407:Tumor Cells, Cultured
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D016718:Arachidonic Acid