Tissue ACE phenotyping in lung cancer


Autoři: Sergei M. Danilov aff001;  Roman Metzger aff004;  Eckhard Klieser aff005;  Karl Sotlar aff005;  Ilya N. Trakht aff006;  Joe G. N. Garcia aff002
Působiště autorů: Department of Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago, IL, United States of America aff001;  Department of Medicine, University of Arizona Health Sciences, Tucson, AZ, United States of America aff002;  Medical Center, Moscow University, Moscow, Russia aff003;  Department of Pediatric and Adolescent Surgery, Paracelsus Medical University, Salzburg, Austria aff004;  Institute of Pathology, Paracelsus Medical University, University Hospital Salzburg, Salzburg, Austria aff005;  Department of Medicine, Columbia University, New York, NY, United States of America aff006
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226553

Souhrn

Background

Pulmonary vascular endothelium is the main metabolic site for Angiotensin I-Converting Enzyme (ACE)-mediated degradation of several biologically-active peptides (angiotensin I, bradykinin, hemo-regulatory peptide Ac-SDKP). Primary lung cancer growth and lung cancer metastases decrease lung vascularity reflected by dramatic decreases in both lung and serum ACE activity. We performed precise ACE phenotyping in tissues from subjects with lung cancer.

Methodology

ACE phenotyping included: 1) ACE immunohistochemistry with specific and well-characterized monoclonal antibodies (mAbs) to ACE; 2) ACE activity measurement with two ACE substrates (HHL, ZPHL); 3) calculation of ACE substrates hydrolysis ratio (ZPHL/HHL ratio); 4) the pattern of mAbs binding to 17 different ACE epitopes to detect changes in ACE conformation induced by tumor growth (conformational ACE fingerprint).

Results

ACE immunostaining was dramatically decreased in lung cancer tissues confirmed by a 3-fold decrease in ACE activity. The conformational fingerprint of ACE from tumor lung tissues differed from normal lung (6/17 mAbs) and reflected primarily higher ACE sialylation. The increase in ZPHL/HHL ratio in lung cancer tissues was consistent with greater conformational changes of ACE. Limited analysis of the conformational ACE fingerprint in normal lung tissue and lung cancer tissue form the same patient suggested a remote effect of tumor tissue on ACE conformation and/or on “field cancerization” in a morphologically-normal lung tissues.

Conclusions/Significance

Local conformation of ACE is significantly altered in tumor lung tissues and may be detected by conformational fingerprinting of human ACE.

Klíčová slova:

Adenocarcinoma of the lung – Adenocarcinomas – Blood – Lung and intrathoracic tumors – Non-small cell lung cancer – Secondary lung tumors – Small cell lung cancer – Squamous cell lung carcinoma


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