| First Author | Liang P | Year | 2019 |
| Journal | J Natl Cancer Inst | Volume | 111 |
| Issue | 1 | Pages | 52-59 |
| PubMed ID | 30202902 | Mgi Jnum | J:270009 |
| Mgi Id | MGI:6274432 | Doi | 10.1093/jnci/djy125 |
| Citation | Liang P, et al. (2019) Role of Host GPR120 in Mediating Dietary Omega-3 Fatty Acid Inhibition of Prostate Cancer. J Natl Cancer Inst 111(1):52-59 |
| abstractText | Background: GPR120, a G protein-coupled receptor for long-chain polyunsaturated fatty acids (FAs), mediates the anti-inflammatory effects of omega-3 (omega-3) FAs. We investigated whether host or tumor GPR120 plays a role in the anti-prostate cancer effects of omega-3 FAs. Methods: MycCap prostate cancer allografts were grown in immunocompetent wild-type (WT) and GPR120 knockout (KO) mice fed omega-3 (fish oil) or omega-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 omega-3 FAs decreased MycCap allograft tumor growth (mean [SD] final tumor volume omega-6 = 491 [437] mm3 vs omega-3 = 127 [77] mm3, P = .04), whereas in global GPR120KO mice (n = 7 per group) omega-3 FAs had no anticancer effects. Dietary omega-3 FAs inhibited GPR120KO-MycCaP allografts grown in WT mice (n = 8 per group; mean [SD] final tumor volume omega-6 = 776 [767] mm3 vs omega-3 = 36 [34] mm3, 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 omega-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-omega-3 diet (r = -.57, P = .04). Conclusions: Host GPR120 plays a central role in the anti-prostate cancer effects of dietary omega-3 FAs. Future studies are required to determine if the anticancer effects of omega-3 FAs are mediated through inhibition of M2-like macrophages and if host GPR120 status predicts anticancer effects of dietary omega-3 FAs in men with prostate cancer. |
