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The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we inves...

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Autores principales: Rymaszewski, Amy L., Tate, Everett, Yimbesalu, Joannes P., Gelman, Andrew E., Jarzembowski, Jason A., Zhang, Hao, Pritchard, Kirkwood A., Vikis, Haris G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074819/
https://www.ncbi.nlm.nih.gov/pubmed/24821130
http://dx.doi.org/10.3390/cancers6021111
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author Rymaszewski, Amy L.
Tate, Everett
Yimbesalu, Joannes P.
Gelman, Andrew E.
Jarzembowski, Jason A.
Zhang, Hao
Pritchard, Kirkwood A.
Vikis, Haris G.
author_facet Rymaszewski, Amy L.
Tate, Everett
Yimbesalu, Joannes P.
Gelman, Andrew E.
Jarzembowski, Jason A.
Zhang, Hao
Pritchard, Kirkwood A.
Vikis, Haris G.
author_sort Rymaszewski, Amy L.
collection PubMed
description Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.
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spelling pubmed-40748192014-06-30 The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development Rymaszewski, Amy L. Tate, Everett Yimbesalu, Joannes P. Gelman, Andrew E. Jarzembowski, Jason A. Zhang, Hao Pritchard, Kirkwood A. Vikis, Haris G. Cancers (Basel) Article Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting. MDPI 2014-05-09 /pmc/articles/PMC4074819/ /pubmed/24821130 http://dx.doi.org/10.3390/cancers6021111 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Rymaszewski, Amy L.
Tate, Everett
Yimbesalu, Joannes P.
Gelman, Andrew E.
Jarzembowski, Jason A.
Zhang, Hao
Pritchard, Kirkwood A.
Vikis, Haris G.
The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development
title The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development
title_full The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development
title_fullStr The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development
title_full_unstemmed The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development
title_short The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development
title_sort role of neutrophil myeloperoxidase in models of lung tumor development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074819/
https://www.ncbi.nlm.nih.gov/pubmed/24821130
http://dx.doi.org/10.3390/cancers6021111
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