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Neutrophils are required for 3-methylcholanthrene-initiated, butylated hydroxytoluene-promoted lung carcinogenesis. Mol Carcinog 2012 Dec;51(12):993-1002

Date

10/19/2011

Pubmed ID

22006501

Pubmed Central ID

PMC3389580

DOI

10.1002/mc.20870

Scopus ID

2-s2.0-84867746013   13 Citations

Abstract

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 M

Authors

Pengyuan Liu PhD Adjunct Professor in the Physiology department at Medical College of Wisconsin
Ming You MD, PhD Associate Provost, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Butylated 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
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d