Research Papers:

Tissue ACE phenotyping in prostate cancer

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

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Oncotarget. 2019; 10:6349-6361. https://doi.org/10.18632/oncotarget.27276

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Sergei M. Danilov1,2,3, Alexey V. Kadrev3, Olga V. Kurilova3, Victoria E. Tikhomirova4, Olga V. Kryukova4, Vadim N. Mamedov5, David M. Kamalov3, Natalia V. Danilova3, Dmitry A. Okhobotov3,5, Nurshat M. Gayfullin3,5, Valery V. Evdokimov6, Boris J. Alekseev6, Olga A. Kost4, Larisa M. Samokhodskaya3 and Armais A. Kamalov3,5

1 Department of Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago, IL, Chicago, USA

2 Department of Medicine, University of Arizona, Tucson, AZ, USA

3 Medical Research and Educational Center, Lomonosov Moscow State University, Moscow, Russia

4 Department of Chemistry, Lomonosov Moscow State University, Moscow, Russia

5 Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow, Russia

6 Lopatkin Research Institute of Urology and Interventional Radiology, Moscow, Russia

Correspondence to:

Sergei M. Danilov,email: [email protected]

Keywords: angiotensin I-converting enzyme; prostate cancer; benign prostate hyperplasia; CD143; monoclonal antibodies

Abbreviations: ACE: angiotensin-converting enzyme; mAbs: monoclonal antibodies; ZPHL: carbobenzoxy-L-phenylalanyl-L-histidyl-L-leucine; HHL: hippuryl-L-histidyl-L-leucine; PBS: phosphate buffered saline

Received: May 29, 2019     Accepted: August 27, 2019     Published: October 29, 2019


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.

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