Abstract 1499: Periprostatic fat from obese patients promotes prostate cancer growth

Abstract

Abstract Background: Obesity, particularly visceral obesity, increases the risk of prostate cancer (PCa) progression. However, the mechanism of this remains unclear. Here, we hypothesized that the visceral periprostatic fat (PPF) from obese PCa patients stimulates progression as compared to subcutaneous fat (SQF) or PPF from lean patients. Methods: PPF and SQF were collected from PCa patients. MTT assays were performed on endothelial and PC-3 PCa cells to test proliferative activity in explant culture tissue conditioned media (CM). Angiogenesis was evaluated ex vivo using MR to generate T2 relaxation times from a series of T2-weighted spin-echo images (Bruker 14.1 T imager). Results: PPF CM from an obese patient increased endothelial cell proliferation ∼5 times that of PPF CM from a lean patient (P<0.01). In contrast, SQF CM, from lean or obese patients, showed only minimal activity. When tested on PC-3 cells, SQF CM from obese or lean patients only weakly promoted proliferation. In contrast, PPF CM significantly induced proliferation; however, obese PPF CM was significantly higher than that of lean PPF CM (P<0.05). Interestingly, the MR data revealed key differences between PPF and SQF and between lean and obese fat (Table 1). In all patients, the PPF T2 was lower than that of the SQF (P<0.01). And, the PPF T2 from obese patients was lower than that of lean patients. A lower T2 reflects elevated hemoglobin levels and thus could serve as an indirect measure of vascularity. And, our data suggest that vascularity is increased in obese PPF as compared to SQF and lean PPF tissues. Conclusions: Our data reveal that PPF has increased angiogenic and tumorigenic capacity as compared to SQF and this potential is markedly increased by the presence of obesity. Adipokines and/or other molecules expressed by the PPF may modify the PCa microenvironment to potentiate tumor growth. Our results also support the potential use of MR clinically as a non-invasive test of the angiogenic potential of PPF in PCa patients. 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 1499. doi:1538-7445.AM2012-1499