Bioenergetic signature and oxidative stress as markers of Prostate Cancer progression

Abstract

The prostatic morphology and physiology have been analyzed, specially due to large occurrence of prostatic diseases, including the prostate cancer (PC). Different studies have demonstrated the importance of androgens and estrogens at the development and maintenance of the prostate gland and indicated that the joint action of those hormones and their receptors may trigger prostate lesions. Cancer cells face two distinct metabolic challenges: how to modify their cellular metabolism to support enhanced cell growth and proliferation, and how to engage strategies of metabolic adaptation to survive environmental fluctuations and the availability of nutrients and oxygen. As all cancer cells are dependent on this change in metabolism, these altered pathways represent attractive therapeutic targets. Further, the oxygen consumption by tumor cells may be directly associated with the generation of reactive oxygen species (ROS). These facts make the study of the association among PC, energetic metabolism, ROS and steroids hormones receptors an important progress to the knowledge of these tumor type, mainly when it relates these events with the normal basal conditions of the cell. Therefore, the aims of this are to characterize and to correlate the energetic metabolism, the ROS and the sexual steroids hormones receptors as a clinical-pathologic prognostic of the low, intermediate and high-grades of prostate adenocarcinoma. In this study, 40 peripheral prostatic zone samples are going to be obtained from 60 to 90-year-old patients with and without prostatic lesions hospitalized in University of Campinas (UNICAMP) School of Medicine's teaching Hospital. The prostatic samples are going to be divided into 4 groups (10 samples per group): Normal Group (no lesions), Low-grade Adenocarcinoma Group (Gleason score d 6), Intermediate grade Adenocarcinoma Group (Gleason score 6 - 7) and High-grade Adenocarcinoma Group (Gleason score e 7). The prostatic samples from Normal Group are going to be obtained from necropsied patients without diagnosis of prostatic or other urological diseases. In addition, the prostatic samples from Low, Intermediate and High-grades Adenocarcinoma Groups are going to be obtained from patients submitted to needle biopsy and/ or radical prostatectomy. All samples from Normal and Adenocarcinoma (Low, Intermediate and High-grades) groups are going to be obtained from the parasagittal midline of the posterior surface of the prostatic peripheral zone and submitted to histopathological and immunohistochemical analyses. In this project, we expect to get more knowledge about the energetic metabolism and its relations with the ROS synthesis enzymes and with the sexual steroids hormones receptors, so that relations can be an important tool for the diagnosis and monitoring of the patients with prostate cancer. (AU)