Grant Abstract: UCLA SPORE in Prostate Cancer

Grant Number: 5P50CA092131-14
PI Name: Reiter
Project Title: UCLA SPORE in Prostate Cancer

Abstract: Our present SPORE funded project is evaluating the potential of a low-fat diet with fish oil to delay prostate cancer progression in men on active surveillance. The mechanistic studies of our SPORE funded project focus on the role of the GPR120 receptor in mediating the anticancer effects of fish oil. Of great interest, our preliminary studies suggest that omega-3 fatty acids (?-3 FAs) may inhibit prostate cancer progression by modulating tumor associated immune cells. We found that dietary ?-3 FAs delayed prostate cancer growth in a fully immunocompetent prostate cancer allograft mouse model, and altered expression of immune cell populations known to play a role in prostate cancer progression. In this administrative amendment we propose to investigate the effect of ?-3 FAs on tumor associated immune cell function and determine the role of PPAR? and associated pathways on the anti-inflammatory and anticarcinogenic effect of ?-3 FAs. We hypothesize that activating inflammatory cell nuclear receptor PPAR? by DHA will modulate the function of tumor infiltrating immune cells leading to antiproliferative and pro-apoptotic effects on prostate cancer. Our specific aims are:
1. Determine the effect of dietary ?-3 FAs on immune cell infiltration and function in MycCap prostate tumor allografts in fully immunocompetent mice.
2. Determine if the immunomodulatory effects of ?-3 FAs identified in Aim 1 are mediated through PPAR? associated pathways.
3. Determine if ?-3 FA treated immune cells identified in Aim 1 have a direct effect on prostate cancer biology.
Omega-3 and omega-6 diets will be fed to immunocompetent mice bearing MycCaP prostate tumors. Flow cytometry and fluorescence-activated cell sorting and RT qPCR will be used to determine the effects of the diets on the function of immune cells invading the MycCaP tumors. In vitro studies will further define if the immunomodulatory effects of ?-3 FAs are mediated through PPAR?.

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