Influence of omega-6 PUFA arachidonic acid and bone marrow adipocytes on metastatic spread from prostate cancer

M. D. Brown, C. Hart, E. Gazi, P. Gardner, N. Lockyer, N. Clarke

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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 (3998514.4 vs 932265.8; P0.00002), which stimulated greater PC-3 invasion than free AA (22 408.5607.4 vs 16 236313.9; P0.01111) 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. Conclusion: 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. © 2010 Cancer Research UK. All rights reserved.
Original languageEnglish
Pages (from-to)403-413
Number of pages10
JournalBritish Journal of Cancer
Issue number2
Publication statusPublished - Jan 2010


  • Adipocytes
  • Arachidonic acid
  • Bone marrow
  • Lipid
  • Metastasis
  • Prostate cancer

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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