Arachidonic acid induction of Rho-mediated transendothelial migration in prostate cancer.

Mick David Brown, Jo-An Roulson, Claire Alexandre Hart, Thomas Tawadros, Noel William Clarke

Research output: Contribution to journalArticlepeer-review


Background:Bone metastases in prostate cancer (CaP) result in CaP-related morbidity/mortality. The omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA) and lipophilic statins affect metastasis-like behaviour in CaP cells, regulating the critical metastatic step of CaP migration to the bone marrow stroma.Methods:Microscopic analysis and measurement of adhesion and invasion of CaP cells through bone marrow endothelial cells (BMEC) was undertaken with AA stimulation and/or simvastatin (SIM) treatment. Amoeboid characteristics of PC-3, PC3-GFP and DU-145 were analysed by western blotting and Rho assays.Results:The CaP cell lines PC-3, PC3-GFP and DU-145 share the ability to migrate across a BMEC layer. Specific amoeboid inhibition decreased transendothelial migration (TEM). AA stimulates amoeboid characteristics, driven by Rho signalling. Selective knock-down of components of the Rho pathway (RhoA, RhoC, Rho-associated protein kinase 1 (ROCK1) and ROCK2) showed that Rho signalling is crucial to TEM. Functions of these components were analysed, regarding adhesion to BMEC, migration in 2D and the induction of the amoeboid phenotype by AA. TEM was reduced by SIM treatment of PC3-GFP and DU-145, which inhibited Rho pathway signalling.Conclusions:AA-induced TEM is mediated by the induction of a Rho-driven amoeboid phenotype. Inhibition of this cell migratory process may be an important therapeutic target in high-risk CaP.
Original languageEnglish
Pages (from-to)2099-2108
Number of pages9
JournalB J C
Issue number8
Publication statusPublished - 15 Apr 2014


  • prostate cancer
  • metastasis
  • omega 6
  • arachidonic acid
  • amoeboid
  • Rho
  • EphA2

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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