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Tissue ACE phenotyping in prostate cancer.

Sergei M Danilov1,2,3, Alexey V Kadrev3, Olga V Kurilova3

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

Oncotarget
|November 8, 2019
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Summary

Prostate cancer (PC) significantly reduces angiotensin-converting enzyme (ACE) production. ACE phenotyping in prostate biopsies may offer early detection of PC and differentiate it from benign prostate hyperplasia (BPH).

Keywords:
CD143angiotensin I-converting enzymebenign prostate hyperplasiamonoclonal antibodiesprostate cancer

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Area of Science:

  • Biochemistry
  • Oncology
  • Urology

Background:

  • Prostate epithelial cells normally express high levels of angiotensin-converting enzyme (ACE), leading to significantly elevated ACE concentrations in seminal fluid compared to plasma.
  • Prostate cancer (PC) is characterized by a decrease in ACE production within prostate tissues due to the replacement of specialized epithelial cells by tumor cells.

Purpose of the Study:

  • To characterize the status of ACE in prostate tissues from patients with benign prostate hyperplasia (BPH) and PC using a novel ACE phenotyping approach.
  • To evaluate the potential of ACE phenotyping for early diagnosis and differential diagnosis of BPH and PC.

Main Methods:

  • ACE phenotyping was employed, assessing ACE activity with two substrates (HHL and ZPHL), the ZPHL/HHL hydrolysis ratio, the ratio of immunoreactive ACE protein to ACE activity, and the ACE conformational fingerprint via mAb binding patterns.
  • These parameters were analyzed in prostate tissues from patients diagnosed with BPH and PC.

Main Results:

  • ACE activity was dramatically decreased in PC tissues, accompanied by an increased ratio of immunoreactive ACE protein to ACE activity.
  • The ZPHL/HHL ratio, a catalytic parameter, increased in prostate tissues from all PC patients but remained unchanged in most BPH patients.
  • Some BPH patients exhibited decreased ACE activity, increased immunoreactive ACE protein/ACE activity, and altered ZPHL/HHL ratios, suggesting potential early indicators of PC.

Conclusions:

  • ACE phenotyping reveals significant alterations in ACE characteristics in prostate tissues affected by PC.
  • The observed changes in ACE activity, protein levels, and conformational fingerprint suggest that ACE phenotyping could serve as an effective tool for the early diagnosis of prostate cancer.
  • ACE phenotyping shows promise for differentiating between BPH and PC, potentially identifying PC at earlier stages than conventional histology.