Role of Host GPR120 in Mediating Dietary Omega-3 Fatty Acid Inhibition of Prostate Cancer
Menée à l'aide d'allogreffes de cancer de la prostate sur deux modèles murins, cette étude analyse le rôle du récepteur GPR120 dans l'inhibition de la croissance tumorale par les acides gras oméga-3 d'origine alimentaire
Background : GPR120, a G protein–coupled receptor for long-chain polyunsaturated fatty acids (FAs), mediates the anti-inflammatory effects of omega-3 (
ω-3) FAs. We investigated whether host or tumor GPR120 plays a role in the anti
–prostate cancer effects of
ω-3 FAs. Methods
:
MycCap prostate cancer allografts were grown in immunocompetent wild-type (WT) and GPR120 knockout (KO) mice fed ω-3 (fish oil) or ω-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
ω-3 FAs decreased MycCap allograft tumor growth (mean [SD] final tumor volume ω-6 = 491 [437] mm3 vs ω-3 = 127 [77] mm3, P
= .04), whereas in global GPR120KO mice (n = 7 per group)
ω-3 FAs had no anticancer effects. Dietary ω-3 FAs inhibited GPR120KO-MycCaP allografts grown in WT mice (n
= 8 per group; mean [SD] final tumor volume
ω-6 = 776 [767] mm3 vs ω-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
ω-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-
ω-3 diet (r =
–.57, P = .04). Conclusions : Host GPR120 plays a central role in the anti–prostate cancer effects of dietary
ω-3 FAs. Future studies are required to determine if the anticancer effects of ω-3 FAs are mediated through inhibition of M2-like macrophages and if host GPR120 status predicts anticancer effects of dietary ω-3 FAs in men with prostate cancer.