Role of Host GPR120 in Mediating Dietary Omega-3 Fatty Acid Inhibition of Prostate Cancer

Background GPR120, a G protein-coupled receptor for long-chain polyunsaturated fatty acids (FAs), mediates the anti-inflammatory effects of omega-3 (-3) FAs. We investigated whether host or tumor GPR120 plays a role in the anti-prostate cancer effects of -3 FAs. Methods MycCap prostate cancer allografts were grown in immunocompetent wild-type (WT) and GPR120 knockout (KO) mice fed -3 (fish oil) or -6 (corn oil) diets. Immune cell infiltration was quantified by flow cytometry, and gene expression of immune cell markers in isolated tumor-associated macrophages (TAMs) was quantified by quantitative real-time polymerase chain reaction. Archived tissue from a fish oil intervention trial was used to correlate gene expression of GPR120 with cell cycle progression (CCP) genes and Ki67 index (n=11-15 per group). All statistical tests were two-sided. Results In WT mice (n=7 per group), dietary -3 FAs decreased MycCap allograft tumor growth (mean [SD] final tumor volume -6 = 491 [437] mm(3) vs -3 = 127 [77] mm(3), P=.04), whereas in global GPR120KO mice (n=7 per group) -3 FAs had no anticancer effects. Dietary -3 FAs inhibited GPR120KO-MycCaP allografts grown in WT mice (n=8 per group; mean [SD] final tumor volume -6 = 776 [767] mm(3) vs -3 = 36 [34] mm(3), P=.02). Omega-3 FA treatment decreased the number of M2-like TAMs in tumor tissue and gene expression of M2 markers in isolated TAMs compared with -6 controls in WT (n=7 per group) but not in GPR120KO mice (n=7 per group). In human tissue, higher expression of stromal GPR120 correlated with greater reduction in expression of CCP genes in men with prostate cancer on a high--3 diet (r = -.57, P=.04). Conclusions Host GPR120 plays a central role in the anti-prostate cancer effects of dietary -3 FAs. Future studies are required to determine if the anticancer effects of -3 FAs are mediated through inhibition of M2-like macrophages and if host GPR120 status predicts anticancer effects of dietary -3 FAs in men with prostate cancer.