Abstract P1-01-10: Expression of adipocyte fatty acid binding protein promotes obesity-associated mammary tumor growth

Abstract

Abstract Background: Obesity increases the risk of many types of cancer, including breast cancer. The underlying mechanisms that drive obesity-related breast cancer remain unclear. Fatty Acid Binding Proteins (FABPs) are a family of cytosolic proteins which are organ specific and coordinate lipid transportation. Adipocyte FABP (A-FABP) is highly expressed in adipose tissues and may provide a link to obesity-associated breast cancer risk. We previously observed that A-FABP serum levels were associated with obesity, and decreased with surgically induced weight loss. In this report, we evaluate the role of A-FABP in promoting obesity-associated mammary tumor growth. Hypothesis: Deficiency of A-FABP in mice decreases obesity-associated mammary tumor progression. Methods: Weaned wild type control and A-FABP-deficient (genetically depleted A-FABP-/-) female mice (n=15/group) were randomly grouped and fed either a high fat diet (HFD) (60% fat) or a low fat diet (LFD) (10% fat). After 6 months on the diets, serum was collected from the tail vein and measured for levels of circulating A-FABP by ELISA. E0771 mammary tumor cells (0.5x106/mouse) were injected into the mammary fat pad and tumor volume measured at 3-day intervals. The student's t-test was used to compare A-FABP levels and ANOVA to compare tumor sizes in the lean and obese mice. Results: HFD-fed control mice exhibited a significant increase in body weight (31.5±2.13g) compared to LFD-fed control mice (19.86±0.36) (p<0.01). Serum levels of A-FABP were correspondingly elevated in obese (104.9±8.3 ng/ml) vs. lean controls (31.8±5.4 ng/ml) (p<0.01). Interestingly, although A-FABP deficient mice fed a HFD were more obese than HFD-fed control mice (final body weight 43.4g vs. 31.5 g) (p<0.05), tumor growth in the A-FABP deficient mice was significantly less than in controls (p<0.0001), suggesting that A-FABP expression is critical for obesity-associated mammary tumor growth. Long term tumor growth in lean A-FABP deficient vs. control mice was not significantly different. Thus, A-FABP deficiency appears to uncouple obesity and mammary tumor growth in HFD-induced obese mice. Impact: A-FABP is associated with obesity related breast/mammary cancer, and appears to be an important driver of tumor development. Downregulation of this protein may be useful to prevent and/or treat these tumors. Citation Format: Sauter ER, Li B, Hao J, Kong M. Expression of adipocyte fatty acid binding protein promotes obesity-associated mammary tumor growth [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 P1-01-10.