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

Wake Forest University Health Sciences, Winston-Salem NC

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Abstract

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