Effect of Dietary Omega-3 Fatty Acid Supplement on Prostate Cancer Metastasis

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Metastasis, especially to the bone, is the most significant cause of morbidity and mortality in prostate cancer patients. Therefore, development of relevant metastasis models for prostate cancer is of critical importance for delineating the molecular mechanism underlining this process. In our preliminary studies, we showed that omega-3 (n-3) polyunstatured fatty acids (PUFAs) can inhibit the progression of prostate cancer in a Pten knockout mouse model, and increase survival of tumor-bearing animals. However, the effect of n-3 PUFA on prostate cancer metastasis was not assessed. Epidemiological data suggest that higher consumption of fish, a rich source of n-3 PUFA, is strongly associated with a reduced risk of metastatic prostate cancer. In this proposal, we will develop an animal model for spontaneous prostate cancer metastasis, and use this model to determine the potential effect of n-3 PUFA on metastasis. Aim 1. Develop a quantitative, live-observable model of prostate cancer metastasis. Enhanced yellow fluorescent protein (EYFP) and lacZ markers will be used for live-monitoring and quantification of tumor burden, respectively, at the primary tumor site and at the site of metastases. The transgenes will be introduced into prostate-specific Pten knockout mice that mimic well the clinical course of human prostate cancer, from prostatic intraepithelial neoplasia, carcinoma in situ, invasive carcinoma to metastasis. The EYFP and LacZ markers will be expressed only in prostate tumor cells. Importantly, their levels of expression will not be reduced or extinguished overtime or when prostate tumor cells metastasize to other organs such as the bone, lung, and lymph nodes. Aim 2. Determine the effect of dietary n-3 fatty acid supplement on prostate cancer metastasis. Animals will be fed with diets containing various amounts of n-3 PUFA. Development of cancer in the prostate and metastasis in the lung, inguinal lymph nodes and tibia/femur will be monitored. Tumor burden will be quantified.