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Neutrophils are required for 3‐methylcholanthrene‐initiated, butylated hydroxytoluene‐promoted lung carcinogenesis
Author(s) -
Vikis Haris G.,
Gelman Andrew E.,
Franklin Andrew,
Stein Lauren,
Rymaszewski Amy,
Zhu Jihong,
Liu Pengyuan,
Tichelaar Jay W.,
Krupnick Alexander S.,
You Ming
Publication year - 2012
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20870
Subject(s) - carcinogenesis , biology , chemokine , butylated hydroxytoluene , cxcl1 , cancer research , methylcholanthrene , lung , immunology , carcinogen , inflammation , medicine , biochemistry , antioxidant , gene
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. © 2011 Wiley Periodicals, Inc.