Effects of dietary omega-3 fatty acids on orthotopic prostate cancer progression, tumor associated macrophages, angiogenesis and T-cell activation-dependence on GPR120

Background The antiprostate cancer effects of dietary omega-3 fatty acids (FAs) were previously found to be dependent on host G-protein coupled receptor 120 (GPR120). Using an orthotopic tumor model and an ex-vivo model of bone marrow derived M2-like macrophages, we sought to determine if omega-3 FAs inhibit angiogenesis and activate T-cells, and if these effects are dependent on GPR120. Methods Gausia luciferase labeled MycCaP prostate cancer cells (MycCaP-Gluc) were injected into the anterior prostate lobe of FVB mice. After established tumors were confirmed by blood luminescence, mice were fed an omega-3 or omega-6 diet. Five weeks after tumor injection, tumor weight, immune cell infiltration and markers of angiogenesis were determined. An ex-vivo co-culture model of bone marrow derived M2-like macrophages from wild-type or GPR120 knockout mice with MycCap prostate cancer cells was used to determine if docosahexanoic acid (DHA, omega-3 FA) inhibition of angiogenesis and T-cell activation is dependent on macrophage GPR120. Results Feeding an omega-3 diet significantly reduced orthotopic MycCaP-Gluc tumor growth relative to an omega-6 diet. Tumors from the omega-3 group had decreased M2-like macrophage infiltration and decreased expression of angiogenesis factors. DHA significantly inhibited M2 macrophage-induced endothelial tube formation and reversed M2 macrophage-induced T-cell suppression, and these DHA effects were mediated, in part, by M2 macrophage GPR120. Conclusion Omega-3 FAs delayed orthotopic tumor growth, inhibited M2-like macrophage tumor infiltration, and inhibited M2-like macrophage-induced angiogenesis and T-cell suppression. Given the central role of M2-like macrophages in prostate cancer progression, GPR120-dependent omega-3 FA inhibition of M2-like macrophages may play an important role in prostate cancer therapeutics.

Automated summary

This study aimed to investigate whether dietary omega-3 fatty acids (FAs) inhibit angiogenesis and activate T-cells, and whether these effects are dependent on G-protein coupled receptor 120 (GPR120). The results showed that omega-3 FAs delayed tumor growth, inhibited M2-like macrophage infiltration and angiogenesis, and reversed M2-like macrophage-induced T-cell suppression, and these effects were mediated, in part, by macrophage GPR120.