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

Research output: Contribution to journalArticle

13 Scopus 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.

Original languageEnglish
Pages (from-to)993-1002
Number of pages10
JournalMolecular Carcinogenesis
Volume51
Issue number12
DOIs
StatePublished - Dec 1 2012

Keywords

  • KC
  • Lung
  • Neutrophils
  • T cells
  • Tumor

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    Vikis, H. G., Gelman, A. E., Franklin, A., Stein, L., Rymaszewski, A., Zhu, J., Liu, P., Tichelaar, J. W., Krupnick, A. S., & You, M. (2012). Neutrophils are required for 3-methylcholanthrene-initiated, butylated hydroxytoluene-promoted lung carcinogenesis. Molecular Carcinogenesis, 51(12), 993-1002. https://doi.org/10.1002/mc.20870