The role of neutrophil myeloperoxidase in models of lung tumor development. Cancers (Basel) 2014 May 09;6(2):1111-27
Date
05/14/2014Pubmed ID
24821130Pubmed Central ID
PMC4074819DOI
10.3390/cancers6021111Scopus ID
2-s2.0-84901207748 (requires institutional sign-in at Scopus site) 72 CitationsAbstract
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.
Author List
Rymaszewski AL, Tate E, Yimbesalu JP, Gelman AE, Jarzembowski JA, Zhang H, Pritchard KA Jr, Vikis HGAuthors
Jason A. Jarzembowski MD, PhD Sr Associate Dean, CEO CSG, Professor in the Pathology department at Medical College of WisconsinKirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin
Amy Rymaszewski PhD Research Scientist I in the Pediatrics department at Medical College of Wisconsin
