Tissue ACE phenotyping in lung cancer
| Autor: | Eckhard Klieser, Roman Metzger, Ilya Trakht, Karl Sotlar, Joe G.N. Garcia, Sergei M. Danilov |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Lung Neoplasms Physiology Squamous Cell Lung Carcinoma Lung and Intrathoracic Tumors Small Cell Lung Cancer Epitopes chemistry.chemical_compound 0302 clinical medicine Adenocarcinomas Carcinoma Non-Small-Cell Lung Medicine and Health Sciences Lung Multidisciplinary Adenocarcinoma of the Lung Squamous Cell Carcinomas Antibodies Monoclonal Middle Aged respiratory system Immunohistochemistry Body Fluids Blood Phenotype medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Adenocarcinoma Medicine Female Anatomy Research Article Science Bradykinin Peptidyl-Dipeptidase A Carcinomas 03 medical and health sciences Renin–angiotensin system Adenocarcinoma of the lung medicine Humans Lung cancer Aged business.industry Cancers and Neoplasms Biology and Life Sciences medicine.disease Small Cell Lung Carcinoma Non-Small Cell Lung Cancer 030104 developmental biology chemistry Cancer research Field cancerization Secondary Lung Tumors business |
| Zdroj: | PLoS ONE, Vol 14, Iss 12, p e0226553 (2019) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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