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Tissue ACE phenotyping in lung cancer
Sergei M Danilov1,2,3, Roman Metzger4, Eckhard Klieser5
1Department of Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago, IL, United States of America.
Plos One
|December 27, 2019
Summary
Lung cancer alters Angiotensin I-Converting Enzyme (ACE) conformation and activity. ACE phenotyping reveals significant changes in tumor tissues, offering potential diagnostic insights for lung cancer.
Area of Science:
- Biochemistry
- Oncology
- Pulmonary Medicine
Background:
- The pulmonary vascular endothelium is a key site for Angiotensin I-Converting Enzyme (ACE) activity, involved in metabolizing peptides like angiotensin I and bradykinin.
- Lung cancer development and metastasis are associated with reduced lung vascularity and decreased ACE activity in both lung tissue and serum.
- This study investigates precise ACE phenotyping in lung cancer tissues to understand these alterations.
Purpose of the Study:
- To perform detailed ACE phenotyping in lung cancer tissues.
- To investigate alterations in ACE conformation and activity associated with primary lung cancer and metastases.
- To explore the potential of ACE conformational fingerprinting as a biomarker for lung cancer.
Main Methods:
- ACE immunohistochemistry using specific monoclonal antibodies (mAbs).
- Measurement of ACE activity using two substrates (HHL, ZPHL) and calculation of the ZPHL/HHL ratio.
- Conformational ACE fingerprinting by analyzing mAb binding patterns to 17 distinct ACE epitopes.
Main Results:
- ACE immunostaining and activity were significantly decreased in lung cancer tissues (3-fold reduction).
- The conformational fingerprint of ACE in tumor tissues differed from normal lung tissue, primarily showing increased ACE sialylation.
- An increased ZPHL/HHL ratio in lung cancer tissues indicated greater conformational changes in ACE.
Conclusions:
- Local conformation of ACE is significantly altered in tumor lung tissues.
- Conformational fingerprinting of human ACE can detect these alterations.
- These findings suggest ACE conformation changes may serve as a potential biomarker in lung cancer.
