Epidemiologic and preclinical studies support the role of a low fat diet and fish oil intake for the prevention and treatment of prostate cancer. A prospective pre-prostatectomy trial conducted by our group found that a low-fat diet with fish oil reduced proliferation in prostate cancer epithelium in radical prostatectomy specimens and we found that the RBC membrane omega-6/omega-3 (n-6/n-3) fatty acid ratio correlated with prostate tissue proliferation levels. Our collaborator, Dr. Olefsky, recently identified a G protein coupled receptor (GPR120) on macrophages that mediates the anti-inflammatory effects of EPA and DHA (omega-3 fatty acids in fish oil) and we identified GPR120 in prostate cancer stroma, in neutrophils, and macrophages. Based on these findings, we hypothesize that a low-fat diet with fish oil may confer its anti-inflammatory/anti-proliferative effects on prostate cancer through prostatic stromal GPR120 by modulating the tumor microenvironment. Based on our prior preclinical and clinical studies, we anticipate that a low-fat fish oil (LF/FO) diet will inhibit prostate cancer proliferation in men on active surveillance, that the RBC n-6/n-3 ratio will be a useful blood-based surrogate biomarker to monitor prostate cancer proliferation levels, and that subjects with higher GPR120 levels in prostate tissue will have greater antiproliferative effects in response to fish oil intake. Thus the Aims of our proposal are (1) To determine the contribution of GPR120 to prostate cancer proliferation in archived specimens (2) To determine if a LF/FO diet delays the development of prostate cancer, in part, through the GPR120 receptor by using PTEN and GPR120 knockout mouse models, and (3) to determine the efficacy a LF/FO intervention in men on active surveillance and identify potential surrogate biomarkers for prostate cancer proliferation. We will measure gene expression of GPR120 and related inflammatory pathways in laser captured stromal tissue from our previous clinical trial and correlate these findings with proliferation. A prospective trial will be conducted in 100 men on active surveillance randomized to a low-fat diet with fish oil supplements or to a control group and prostate biopsies will be analyzed for proliferation (Ki-67 index) and GPR120 receptor levels at baseline and 1-year.

Public Health Relevance

Our goal is to determine if a LF/FO diet has the potential to be an effective intervention for men on active surveillance, and to investigate potential biomarkers to predict proliferation in the biopsy tissue. Ultimately this work is designed to elucidate effective nutritional therapies we can offer our patients electing active surveillance for their prostate cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA092131-12
Application #
8760361
Study Section
Special Emphasis Panel (ZCA1-RPRB-M)
Project Start
Project End
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
12
Fiscal Year
2014
Total Cost
$246,421
Indirect Cost
$75,314
Name
University of California Los Angeles
Department
Type
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Vidal, Adriana C; Howard, Lauren E; de Hoedt, Amanda et al. (2018) Neutrophil, lymphocyte and platelet counts, and risk of prostate cancer outcomes in white and black men: results from the SEARCH database. Cancer Causes Control 29:581-588
Vidal, Adriana C; Howard, Lauren E; de Hoedt, Amanda et al. (2018) Obese patients with castration-resistant prostate cancer may be at a lower risk of all-cause mortality: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. BJU Int 122:76-82
Jelinek, David; Flores, Aimee; Uebelhoer, Melanie et al. (2018) Mapping Metabolism: Monitoring Lactate Dehydrogenase Activity Directly in Tissue. J Vis Exp :
Lee, John K; Bangayan, Nathanael J; Chai, Timothy et al. (2018) Systemic surfaceome profiling identifies target antigens for immune-based therapy in subtypes of advanced prostate cancer. Proc Natl Acad Sci U S A 115:E4473-E4482
Mitra, Mithun; Lee, Ha Neul; Coller, Hilary A (2018) Determining Genome-wide Transcript Decay Rates in Proliferating and Quiescent Human Fibroblasts. J Vis Exp :
Zou, Yongkang; Qi, Zhi; Guo, Weilong et al. (2018) Cotargeting the Cell-Intrinsic and Microenvironment Pathways of Prostate Cancer by PI3K?/?/? Inhibitor BAY1082439. Mol Cancer Ther 17:2091-2099
Henning, Susanne M; Galet, Colette; Gollapudi, Kiran et al. (2018) Phase II prospective randomized trial of weight loss prior to radical prostatectomy. Prostate Cancer Prostatic Dis 21:212-220
Miller, Eric T; Salmasi, Amirali; Reiter, Robert E (2018) Anatomic and Molecular Imaging in Prostate Cancer. Cold Spring Harb Perspect Med 8:
Navarro, H├ęctor I; Goldstein, Andrew S (2018) HoxB13 mediates AR-V7 activity in prostate cancer. Proc Natl Acad Sci U S A 115:6528-6529
Mitra, Mithun; Ho, Linda D; Coller, Hilary A (2018) An In Vitro Model of Cellular Quiescence in Primary Human Dermal Fibroblasts. Methods Mol Biol 1686:27-47

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