Abstract B26: A novel dietary advanced glycation end product (AGE) model to assess impact on tumor progression

Abstract

Abstract Advanced glycation end products, or AGEs, and their corresponding receptor, the receptor for AGE (RAGE), have roles in several chronic diseases such as diabetes and cardiovascular disease due to their proinflammatory properties. Recently AGE: RAGE signaling has been implicated in a number of cancers, including prostate and breast cancer; however, how AGE: RAGE signaling effects these cancers has not been elucidated. To examine this, we have developed a novel dietary AGE tumor model. Our regular and AGE (TestDiet DIO 58G7) diets consist of equal %k/cal from fat, protein, and carbohydrate; however, the predominant source of carbohydrate in the control diet is starch and in the AGE diet is sugar. To generate the high-AGE diet we autoclave at 120°C for 15 min. In the high-AGE diet, the autoclaving mimics the cooking process in foods and induces the formation of AGEs, allowing us to observe the effects of chronic AGE consumption on both normal developmental processes as well as tumor formation and progression. Specifically, we have been able to show the impact of this diet during time periods where the breast is more susceptible to chronic AGE consumption, namely the “windows of susceptibility.” Additionally, we have applied this novel dietary model to the RAGE null (-/-) mice to explore the role of AGE:RAGE signaling further. Specifically, we have shown that chronic consumption of a high-AGE diet disrupts normal pubertal growth in the mammary gland through the recruitment of aberrant stroma, including fibroblasts and macrophages, and that these aberrant changes persist into adulthood. We further show that dietary AGEs promote aggressive tumor growth through manipulation of the tumor microenvironment and that this is RAGE dependent. We propose that this dietary model can be used as an in vivo method to examine the impact of dietary AGEs on the TME and as a mechanism for potential therapeutic and preventative strategies. Citation Format: Reid K. Schuster, Bradley A. Krisanits, Jamie Randise, Lourdes M. Nogueira, Kristi Helke, Amanda C. LaRue, David P. Turner, Victoria J. Findlay. A novel dietary advanced glycation end product (AGE) model to assess impact on tumor progression [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B26.