Influence of omega-6 PUFA arachidonic acid and bone marrow adipocytes on metastatic spread from prostate cancer.
BACKGROUND
Prostate cancer (CaP) preferentially metastasises to the bone, and we have previously shown that the poly-unsaturated fatty acid (PUFA) arachidonic acid (AA) is a potent stimulator of CaP invasion. Here we present that AA promotes CaP invasion by inducing bone marrow adipocyte formation.


METHODS
Boyden invasion-chamber assays assessed the ability of dietary oils, their PUFA components, and specific PUFA-loaded adipocytes to induce PC-3 invasion. Lipid transfer and metabolism was followed using deuterated AA and Fourier Transform Infrared spectroscopy (FTIR).


RESULTS
Poly-unsaturated fatty acid constituents, but not their corresponding dietary oils, induced PC-3 invasion. PUFAs induce bone marrow adipocyte (BM-Ad) differentiation with AA inducing higher levels of BM-Ad differentiation, as compared with other PUFAs (3998+/-514.4 vs 932+/-265.8; P=0.00002), which stimulated greater PC-3 invasion than free AA (22 408.5+/-607.4 vs 16 236+/-313.9; P=0.01111) or adipocytes generated in the presence of other PUFAs. In bone marrow co-culture PC-3 and BM-Ad interactions result in direct uptake and metabolism of AA by PC-3 cells, destruction of the adipocyte and subsequent formation of a bone metastasis.


CONCLUSIONS
The data supports the hypothesis that AA not only promotes CaP invasion, it also prepares the 'soil', making it more supportive for implantation and propagation of the migrating metastatic cell.
Brown
M D
MD
Genito-Urinary Cancer Research Group, School of Cancer, Enabling Sciences and Technology, Paterson Institute for Cancer Research, The University of Manchester, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Manchester M20 4BX, UK. mbrown@picr.man.ac.uk
Hart
C
C
Gazi
E
E
Gardner
P
P
Lockyer
N
N
Clarke
N
N
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D016718:Arachidonic Acid / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000503:physiopathology / Q000556:secondary
D043371:Fatty Acids, Omega-6; D016718:Arachidonic Acid