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

  • Prostate Cancer Prostatic Dis. 2022 Sep;25(3):539-546. doi: 10.1038/s41391-021-00440-2.
Pei Liang  1 ,  Susanne M Henning  1 ,  Tristan Grogan  2 ,  David Elashoff  2 ,  Huihui Ye  3 ,  Pinchas Cohen  4 ,  William J Aronson  5  6
Affiliations
  • 1. Department of Urology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
  • 2. Department of Medicine Statistics Core, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • 3. Department of Pathology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
  • 4. Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
  • 5. Department of Urology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. [email protected].
  • 6. VA Medical Center Greater Los Angeles Healthcare System, Los Angeles, CA, USA. [email protected].
PMID: 35075215 DOI: 10.1038/s41391-021-00440-2
Abstract

Background: The antiprostate Cancer effects of dietary ω-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 ω-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 ω-3 or ω-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, ω-3 FA) inhibition of angiogenesis and T-cell activation is dependent on macrophage GPR120.

Results: Feeding an ω-3 diet significantly reduced orthotopic MycCaP-Gluc tumor growth relative to an ω-6 diet. Tumors from the ω-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 ω-3 FA inhibition of M2-like macrophages may play an important role in prostate Cancer therapeutics.

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