Tissue ACE phenotyping in prostate cancer.

Vadim N Mamedov,Sergei M Danilov,Armais A Kamalov,Larisa M Samokhodskaya,Olga A Kost,David M Kamalov,Valery V Evdokimov,Dmitry A Okhobotov,Natalia V Danilova,Victoria E Tikhomirova,Olga V Kryukova,Nurshat M Gayfullin,Boris J Alekseev,Alexey V Kadrev,Olga V Kurilova

doi:10.18632/oncotarget.27276

Abstract

Epithelial cells of prostate express significant level of ACE and, as a result, seminal fluid has 50-fold more ACE than plasma. The substitution of highly specialized prostate epithelial cells by tumor cells results in dramatic decrease in ACE production in prostate tissues. We performed detailed characterization of ACE status in prostate tissues from patients with benign prostate hyperplasia (BPH) and prostate cancer (PC) using new approach- ACE phenotyping, that includes evaluation of: 1) ACE activity with two substrates (HHL and ZPHL); 2) the ratio of the rates of their hydrolysis (ZPHL/HHL ratio); 3) the ratio of immunoreactive ACE protein to ACE activity; 4) the pattern of mAbs binding to different epitopes on ACE – ACE conformational fingerprint - to reveal conformational changes in prostate ACE due to prostate pathology. ACE activity dramatically decreased and the ratio of immunoreactive ACE protein to ACE activity increased in PC tissues. The catalytic parameter, ZPHL/HHL ratio, increased in prostate tissues from all patients with PC, but was did not change for most |BPH patients. Nevertheless, prostate tissues of several patients diagnosed with BPH based on histology, also demonstrated decreased ACE activity and increased immunoreactive ACE protein/ACE activity and ZPHL/HHL ratios, that could be considered as more early indicators of prostate cancer development than routine histology. Thus, ACE phenotyping of prostate biopsies has a potential to be an effective approach for early diagnostics of prostate cancer or at least for differential diagnostics of BPH and PC.

Highlights

Prostate cancer (PC) is the second most common cause of cancer related death for men - worldwide more than a million men are diagnosed with PC each year and about 1/3 of them would die from this disease [1]
Prostate tissues of several patients diagnosed with benign prostate hyperplasia (BPH) based on histology, demonstrated decreased ACE activity and increased immunoreactive ACE protein/ACE activity and ZPHL/HHL ratios, that could be considered as more early indicators of prostate cancer development than routine histology
In the first series of experiments, we performed ACE phenotyping in homogenates of prostate tissues obtained after surgical removal of these tissues from 4 patients with PC and prostate tissues obtained by Trans-URethral Prostatectomy (TURP) of 6 patients with BPH (Supplementary Table 1)

Summary

Introduction

Prostate cancer (PC) is the second most common cause of cancer related death for men - worldwide more than a million men are diagnosed with PC each year and about 1/3 of them would die from this disease [1]. The catalytic parameter, ZPHL/HHL ratio, increased in prostate tissues from all patients with PC, but was did not change for most |BPH patients.

Results

Conclusion