Background: Studies have shown that obesity is associated with a worse breast cancer prognosis. Besides the effect of different stages of diagnosis and co-morbidities, recent data from our published in vitro and retrospective studies suggests that this phenomenon may occur because the obese state promotes a more aggressive cancer phenotype through the cyclooxygenase (COX-2) pathway and its production of prostaglandin E2 (PGE2). The metabolization of omega-3 fatty acids decreases the production of PGE2, and have been shown to have potential benefit to cancer patients by decreasing inflammation-related signaling. Our previous clinical trial showed mixed results in the effect of omega-3 PUFA supplements on PGE2 production in post-menopausal obese women. This led us to the hypothesis that the ratio of omega-3 to omega-6 PUFAs have differential effects on cell types within the tumor microenvironment, impacting cancer cell phenotype.
Approach: In vitro experiments, including wound-healing assays to determine motility, and clonogenic assays to determine overall survival, were performed to determine if exposure to higher ratios of omega-6 to omega-3 fatty acids lead to a more aggressive cancer phenotype. MCF-7 breast cancer cells were treated with the following fatty acid ratios of omega-6 (arachidonic acid (AA)) to omega-3 (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)): 46:1, 20:1, 10:1, and 1.3:1. The wound-healing assays showed greater motility with higher ratios of omega-6 to omega-3 fatty acids conditions and the clonogenic assays showed greater survival with the higher ratios.
Conclusion: These data indicate that lowering ratios of omega-6 to omega-3 fatty acids may lessen the aggressiveness of breast cancer cells and be beneficial to some patients. Studies are on-going to investigate the impact of PUFA ratios on cancer cell phenotype directly, including proliferation and invasion, as well as the indirect effects from modulation of the other cells within the tumor microenvironment, including the macrophages and adipocytes.
Citation Format: Winikka L, Quach D, Harlow B, Brenner A, Munoz N, Tiziani S, deGraffenried L. The ratio of omega-3 to omega-6 PUFAs impact cancer cell phenotype in the tumor microenvironment [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-03-12.