Abstract 5423: Diet induced obesity, inflammation and prostate cancer progression in Hi-Myc mice

Abstract

Abstract Obesity occurs when energy intake exceeds expenditure and is associated with increased risk and/or mortality rates for various types of cancers. In contrast, calorie restriction (CR) has been shown to act as a potent inhibitor of tumorigenesis in many tissues. We have recently reported that diet induced obesity (DIO) enhanced prostate cancer progression in the ventral prostate of the Hi-Myc mice (Blando et al, CAPR, 2011). Significant increases in inflammatory gene expression were observed as well as accumulation of inflammatory cells. In the current study, we have further investigated changes in inflammatory genes as well as cellular changes associated with DIO effects on prostate cancer progression in this mouse model. Initial studies were conducted to look at some of the cell populations that reside 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 (a lipid associated protein that marks adipocytes) 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. Notably, in mice on the DIO diet, many of the glands in the VP were completely surrounded by adipocytes. Additionally, we performed double staining for either 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 both the overweight control and DIO diet groups. This was particularly evident in Hi-Myc mice on the DIO diet. In addition, we have also stained sections of VP from Hi-Myc mice on the different diets 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. These data suggest that IL-23 may play a role not only in driving further inflammatory cell activation (e.g., TH17+/ CD4+ T-cells) but also have direct effects on prostate epithelial cells that facilitate prostate cancer progression. 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 NFkB activation seen in prostate tissues for the same mice and diet group. Thus, Cox-2 and subsequent generation of arachidonic metabolites may also play a role in the effects of DIO on prostate cancer progression in Hi-Myc mice. Collectively, changes in the levels of IL-23R and COX-2 and the elevated presence of inflammatory cells together with changes in the adipose tissue, suggest that the tumor associated microenvironment may play a key role in DIO effects on prostate cancer progression in Hi-Myc mice. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5423. doi:1538-7445.AM2012-5423