# Role of GPR120 and Macrophages in Dietary Omega-3 Fatty Acid Inhibition of Prostate Cancer

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $430,969

## Abstract

PROJECT SUMMARY
Epidemiologic studies and multiple preclinical studies suggest dietary fish oil has the potential to delay prostate
cancer progression. A prospective randomized pre-prostatectomy trial conducted by our group found that
consuming a fish oil (omega-3) supplemented diet resulted in lower proliferation of prostate cancer epithelium
as measured by the Ki-67 index, and decreased Cell Cycle Progression (CCP) Score as compared to a control
Western diet. Both Ki-67 and the CCP Score are associated with prostate cancer progression and mortality,
suggesting potential benefits of consuming a fish oil supplemented diet for prostate cancer patients. In studies
with immunocompetent GPR120 knockout (KO) mice, we recently demonstrated that GPR120, a g-protein
coupled receptor important in the transport of long chain polyunsaturated fatty acids, is required in the host for
the anti-cancer activity of fish oil. Immune suppressive tumor associated macrophages with M2-like
characteristics have been associated with prostate cancer progression and poor prognosis. We also found that
fish oil inhibits the function of M2-like tumor-associated macrophages, and this effect was reversed in the
GPR120 KO mouse. Based on these findings, we hypothesize that a fish oil supplemented diet will delay the
progression of prostate cancer through GPR120 dependent effects on the tumor microenvironment. The Aims of
our proposal are: Aim 1. Determine if dietary omega-3 (ω-3) fatty acids act through GPR120 to inhibit prostate
cancer in a transgenic mouse model and study underlying mechanisms related to M2 macrophage function. Aim
2. Determine if GPR120 dependent host-derived bone marrow cells and myeloid lineage cells are essential for
the anticancer effects of dietary ω-3 FAs. Aim 3. Identify biomarkers in baseline prostate biopsy tissue that
predict responsiveness to a fish oil based dietary intervention by examining prostate biopsy tissue obtained from
an ongoing active surveillance trial in men receiving a fish oil supplemented diet (ω-6: ω-3 ratio of 3:1). We will
accomplish these aims through a series of mechanistic studies using GPR120 knockout and transgenic mouse
models fed diets varying in ω-3 and ω-6 fatty acid content, and studies on prostate biopsy tissue from a Phase
II, dietary intervention, active surveillance trial we are conducting in men with prostate cancer. Significance: Our
proposal sets a new direction for a precision medicine approach for selecting patients more likely to be
responsive to dietary modification based on GPR120 status. By studying the underlying biology of fish oil
anticancer effects through GPR120 and tumor associated macrophages/immune cells, we are establishing a
new field of study, nutritional immunotherapy, that may ultimately lead to innovative nutritional therapies for our
patients with prostate cancer. Our multidisciplinary team of investigators with a longstanding history of successful
collaborations is uniquely suited to achie...

## Key facts

- **NIH application ID:** 10229545
- **Project number:** 5R01CA231219-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** WILLIAM J ARONSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $430,969
- **Award type:** 5
- **Project period:** 2018-09-17 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229545

## Citation

> US National Institutes of Health, RePORTER application 10229545, Role of GPR120 and Macrophages in Dietary Omega-3 Fatty Acid Inhibition of Prostate Cancer (5R01CA231219-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10229545. Licensed CC0.

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