Molecular Diagnostics

BJC Open article

British Journal of Cancer (2010) 102, 403–413. doi:10.1038/sj.bjc.6605481 www.bjcancer.com
Published online 8 December 2009

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

M D Brown1, C Hart1, E Gazi1, P Gardner2, N Lockyer2 and N Clarke1,3,4

  1. 1Genito-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
  2. 2School of Chemical Engineering and Analytical Sciences, Manchester Interdisciplinary Biocentre (MIB), The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK
  3. 3Department of Urology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK
  4. 4Department of Urology, Salford Royal Hope NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK

Correspondence: Dr MD Brown, E-mail: mbrown@picr.man.ac.uk

Received 2 July 2009; Revised 3 November 2009; Accepted 11 November 2009
Advance online publication 8 December 2009

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Abstract

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 (22408.5±607.4 vs 16236±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.

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.

Keywords:

arachidonic acid; bone marrow; prostate cancer; lipid; metastasis; adipocytes

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