Abstract LB-321: Metabolic profiles of periprostatic adipose tissue from prostate cancer patients using MR spectroscopy

Abstract

Abstract Obesity is associated with more aggressive prostate cancer (PCa), with visceral obesity conferring an even higher risk than generalized obesity. However, the mechanism by which obesity fuels PCa progression remains unclear. As an active endocrine organ, adipose tissue contributes to metabolic regulation, and current data suggest that the periprostatic adipose (PPA) tissue from obese PCa patients promotes a tumor permissive microenvironment. We hypothesized that altered lipid metabolism in the PPA tissue may be one mechanism for this activity. In this pilot study, we used MR spectroscopy, a technique which could be readily utilized in vivo to obtain the FA signature of tissues non-invasively, to compare the fatty acid (FA) profiles of PPA tissue and subcutaneous adipose (SQA) tissue taken from PCa patients (n=12). The FA profiles of fat biopsies were obtained from proton MR spectra as follows: PRESS localized spectra were acquired from 8μL voxels in fresh tissue on a 600MHz Bruker Avance spectrometer using recycle time TR 4000ms, echo delay time TE 7.5ms, spectral width 8000Hz, number of complex points 16k, and 256 averages. The various functional groups in FA were identified by peaks appearing at characteristic frequencies (chemical shifts) in the proton spectrum. Peak integrals of FA functional groups were measured from which the fractions of saturated (fS), mono-unsaturated (fM), and poly-unsaturated fatty acids (fP), as well as the fractions of 16C FA (f16C) and 18C FA (f18C) were calculated using published methods (Ren, et al. J. Lipid Res. 49: 2055, 2008). We found that mono-unsaturated FA fraction (fM ∼0.40) was higher than saturated or poly-unsaturated FA fraction in both PPA and SQA tissues from PCa patients. However, in the PPA, fM > fS > fP, whereas in the SQA tissue, fM > fP ∼ fS. In a parallel study, we examined the PPA tissue from obese (ob/ob) mice which develop prostate hyperplasia (unpublished results). In these samples, the mono-unsaturated fatty acids were the predominant FA (fM 0.44) while in wildtype control mice polyunsaturated fatty acids (fP 0.47) were the major FA in the PPA tissue. In the human tissues, while f18C > f16C in both adipose depots, the ratio (f16C/ f18C) was significantly higher in PPA (0.59) than in SQA (0.14). This increased abundance of shorter chain length FA (f16C) suggests that PPA may be metabolically more active than SQA in PCa patients, as shorter chain length FA are mobilized at a higher rate. These data support the potential utility of MR spectroscopy to establish FA profiles of PPA tissue, and in ongoing studies we will test tissues from obese PCa patients and normal controls to determine if differences can be exploited to provide additional diagnostic or prognostic information using this noninvasive technique. (Supported by an award from the Prostate Cancer Foundation, a pilot grant award from NorthShore University HealthSystem, and NIH S10 RR13880) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-321. doi:10.1158/1538-7445.AM2011-LB-321