Neutrophils are required for 3-methylcholanthrene-initiated, butylated hydroxytoluene-promoted lung carcinogenesis. Mol Carcinog 2012 Dec;51(12):993-1002
Date
10/19/2011Pubmed ID
22006501Pubmed Central ID
PMC3389580DOI
10.1002/mc.20870Scopus ID
2-s2.0-84867746013 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
Multiple studies have shown a link between chronic inflammation and lung tumorigenesis. Inbred mouse strains vary in their susceptibility to methylcholanthrene (MCA)-initiated butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated whether neutrophils play a role in strain dependent differences in susceptibility to lung tumor promotion. We observed a significant elevation in homeostatic levels of neutrophils in the lungs of tumor-susceptible BALB/cByJ (BALB) mice compared to tumor-resistant C57BL/6J (B6) mice. Additionally, BHT treatment further elevated neutrophil numbers as well as neutrophil chemoattractant keratinocyte-derived cytokine (KC)/chemokine (C-X-C motif) ligand 1 (Cxcl1) levels in BALB lung airways. Lung CD11c+ cells were a major source of KC expression and depletion of neutrophils in BALB mice resulted in a 71% decrease in tumor multiplicity. However, tumor multiplicity did not depend on the presence of T cells, despite the accumulation of T cells following BHT treatment. These data demonstrate that neutrophils are essential to promote tumor growth in the MCA/BHT two-step lung carcinogenesis model.
Author List
Vikis HG, Gelman AE, Franklin A, Stein L, Rymaszewski A, Zhu J, Liu P, Tichelaar JW, Krupnick AS, You MAuthor
Amy Rymaszewski PhD Research Scientist I in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsButylated Hydroxytoluene
Carcinogens
Cell Transformation, Neoplastic
Female
Flow Cytometry
Immunologic Memory
Immunophenotyping
Lung Neoplasms
Methylcholanthrene
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Neutrophils
T-Lymphocytes
