Abstract 179: Impact of diet-induced obesity on inflamatory pathways during prostate cancer progression in Hi-Myc mice.

Abstract

Abstract We have previously reported that diet induced obesity (DIO) enhanced prostate cancer progression and associated inflammation in the ventral prostate of the Hi-Myc mice (Blando et al, CAPR, 2011). Here, we further investigated changes in inflammatory genes as well as cellular changes associated with DIO effects on prostate cancer progression in the Hi-myc mouse model. Initial studies were conducted to look at specific cell populations that are present in the ventral prostate (VP) of Hi-Myc mice on the 30% CR, overweight control (AIN76A) and DIO diets (60 Kcal% fat). Staining for perilipin revealed that adipocytes were restricted to the periphery of the VP of Hi-Myc mice on the 30% CR diet. In contrast, adipocytes could be seen infiltrating the VP of Hi-Myc mice on the overweight control diet and especially in mice on the DIO diet. In this regard, many of the glands in the VP were completely surrounded by adipocytes. Double IF staining was performed for both perilipin and CD3 (T-lymphocytes) or perilipin and RM0029-11H3 (macrophages). Few if any inflammatory cells were seen in VP of Hi-Myc mice on the 30% CR diet. In contrast, adipocytes and inflammatory cells (both T-cells and macrophages) were seen in close proximity to adipocytes that had infiltrated into the VP in the overweight control group and this was particularly prominent in the DIO diet group. Aditionally, staining for B-cells also showed an increased number in the DIO groups as compared to the control and CR diet groups. Sections of VP from Hi-Myc mice on the different diets were also stained for both the IL-23 receptor (IL-23R) and Cox-2. IL-23R expression was dramatically upregulated in the epithelial cells of the VP from Hi-Myc mice on the DIO compared to the other diet groups. Cox-2 expression was also dramatically upregulated in VP of Hi-Myc on the DIO diet. This finding is consistent with the high level of NFκB activation seen in prostate tissues for the same mice and diet group. The VP from mice on DIO diets also showed an increase in the staining of tissue specific cancer stem cell (CSC) markers (SCA-1 and CD49f) when compared to VP from mice on the overweight control and 30% CR diets. In summary, changes in the levels of IL-23R and COX-2 and the increased presence of inflammatory cells together with changes in the adipose tissue, suggest that the tumor microenvironment may play an important role in DIO effects on prostate cancer progression in Hi-Myc mice. Citation Format: Jorge M. Blando, Kaoru Kiguchi, Irina Fernandez, John DiGiovanni. Impact of diet-induced obesity on inflamatory pathways during prostate cancer progression in Hi-Myc mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 179. doi:10.1158/1538-7445.AM2013-179