Neutrophils are required for 3-methylcholanthrene-initiated, butylated hydroxytoluene-promoted lung carcinogenesis.

Haris G Vikis, Andrew E Gelman, Andrew Franklin, Lauren Stein, Amy Rymaszewski, Jihong Zhu, Pengyuan Liu, Jay W Tichelaar, Alexander S Krupnick, Ming You

Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Molecular carcinogenesis 2012 Dec

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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. Copyright © 2011 Wiley Periodicals, Inc.

Citation

Haris G Vikis, Andrew E Gelman, Andrew Franklin, Lauren Stein, Amy Rymaszewski, Jihong Zhu, Pengyuan Liu, Jay W Tichelaar, Alexander S Krupnick, Ming You. Neutrophils are required for 3-methylcholanthrene-initiated, butylated hydroxytoluene-promoted lung carcinogenesis. Molecular carcinogenesis. 2012 Dec;51(12):993-1002