Neutrophils Are Required for 3-methylcholanthrene-initiated, Butylated Hydroxytoluene-promoted Lung Carcinogenesis

Overview

Journal Mol Carcinog

Specialties Molecular Biology
Oncology

Date 2011 Oct 19

PMID 22006501

Citations 16

Authors

Haris G Vikis

Andrew E Gelman

Andrew Franklin

Lauren Stein

Amy Rymaszewski

Jihong Zhu

Pengyuan Liu

Jay W Tichelaar

Alexander S Krupnick

Ming You

Affiliations

Soon will be listed here.

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.

Citing Articles

Non-Genotoxic and Environmentally Relevant Lower Molecular Weight Polycyclic Aromatic Hydrocarbons Significantly Increase Tumorigenicity of Benzo[]pyrene in a Lung Two-Stage Mouse Model.

Bauer A, Romo D, Friday F, Cho K, Velmurugan K, Upham B Toxics. 2025; 12(12.

PMID: 39771097 PMC: 11679119. DOI: 10.3390/toxics12120882.

Applications of Tert-Butyl-Phenolic Antioxidants in Consumer Products and Their Potential Toxicities in Humans.

Hoang N, Park K Toxics. 2025; 12(12.

PMID: 39771084 PMC: 11679822. DOI: 10.3390/toxics12120869.

TFOS Lifestyle: Impact of cosmetics on the ocular surface.

Sullivan D, da Costa A, Del Duca E, Doll T, Grupcheva C, Lazreg S Ocul Surf. 2023; 29:77-130.

PMID: 37061220 PMC: 11246752. DOI: 10.1016/j.jtos.2023.04.005.

NETworking with cancer: The bidirectional interplay between cancer and neutrophil extracellular traps.

Adrover J, McDowell S, He X, Quail D, Egeblad M Cancer Cell. 2023; 41(3):505-526.

PMID: 36827980 PMC: 10280682. DOI: 10.1016/j.ccell.2023.02.001.

Non-Canonical Functions of Myeloperoxidase in Immune Regulation, Tissue Inflammation and Cancer.

Lockhart J, Sumagin R Int J Mol Sci. 2022; 23(20).

PMID: 36293108 PMC: 9603794. DOI: 10.3390/ijms232012250.

References

Takeichi N, Ba D, Koga Y, Kobayashi H . Immunologic suppression of carcinogenesis in spontaneously hypertensive rats (SHR) with T cell depression. J Immunol. 1983; 130(1):501-5. View

Zarbock A, Allegretti M, Ley K . Therapeutic inhibition of CXCR2 by Reparixin attenuates acute lung injury in mice. Br J Pharmacol. 2008; 155(3):357-64. PMC: 2567887. DOI: 10.1038/bjp.2008.270. View

Gregory A, Houghton A . Tumor-associated neutrophils: new targets for cancer therapy. Cancer Res. 2011; 71(7):2411-6. DOI: 10.1158/0008-5472.CAN-10-2583. View

Baniyash M . Chronic inflammation, immunosuppression and cancer: new insights and outlook. Semin Cancer Biol. 2006; 16(1):80-8. DOI: 10.1016/j.semcancer.2005.12.002. View

Malkinson A . Role of inflammation in mouse lung tumorigenesis: a review. Exp Lung Res. 2005; 31(1):57-82. DOI: 10.1080/01902140490495020. View

Sgambato A, Cittadini A . Inflammation and cancer: a multifaceted link. Eur Rev Med Pharmacol Sci. 2010; 14(4):263-8. View

Bauer A, Dwyer-Nield L, Keil K, Koski K, Malkinson A . Butylated hydroxytoluene (BHT) induction of pulmonary inflammation: a role in tumor promotion. Exp Lung Res. 2001; 27(3):197-216. DOI: 10.1080/019021401300053948. View

Okazaki M, Krupnick A, Kornfeld C, Lai J, Ritter J, Richardson S . A mouse model of orthotopic vascularized aerated lung transplantation. Am J Transplant. 2007; 7(6):1672-9. DOI: 10.1111/j.1600-6143.2007.01819.x. View

Balmain A, Harris C . Carcinogenesis in mouse and human cells: parallels and paradoxes. Carcinogenesis. 2000; 21(3):371-7. DOI: 10.1093/carcin/21.3.371. View

10.

Gungor N, Godschalk R, Pachen D, van Schooten F, Knaapen A . Activated neutrophils inhibit nucleotide excision repair in human pulmonary epithelial cells: role of myeloperoxidase. FASEB J. 2007; 21(10):2359-67. DOI: 10.1096/fj.07-8163com. View

11.

Houghton A . The paradox of tumor-associated neutrophils: fueling tumor growth with cytotoxic substances. Cell Cycle. 2010; 9(9):1732-7. DOI: 10.4161/cc.9.9.11297. View

12.

Fujii M, Miyagi Y, Bessho R, Nitta T, Ochi M, Shimizu K . Effect of a neutrophil elastase inhibitor on acute lung injury after cardiopulmonary bypass. Interact Cardiovasc Thorac Surg. 2010; 10(6):859-62. DOI: 10.1510/icvts.2009.225243. View

13.

Zoumpourlis V, Solakidi S, Papathoma A, Papaevangeliou D . Alterations in signal transduction pathways implicated in tumour progression during multistage mouse skin carcinogenesis. Carcinogenesis. 2003; 24(7):1159-65. DOI: 10.1093/carcin/bgg067. View

14.

Rondini E, Walters D, Bauer A . Vanadium pentoxide induces pulmonary inflammation and tumor promotion in a strain-dependent manner. Part Fibre Toxicol. 2010; 7:9. PMC: 2861012. DOI: 10.1186/1743-8977-7-9. View

15.

Kreisel D, Nava R, Li W, Zinselmeyer B, Wang B, Lai J . In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammation. Proc Natl Acad Sci U S A. 2010; 107(42):18073-8. PMC: 2964224. DOI: 10.1073/pnas.1008737107. View

16.

Santillan A, Camargo Jr C, Colditz G . A meta-analysis of asthma and risk of lung cancer (United States). Cancer Causes Control. 2003; 14(4):327-34. DOI: 10.1023/a:1023982402137. View

17.

Malkinson A, Radcliffe R, Bauer A . Quantitative trait locus mapping of susceptibilities to butylated hydroxytoluene-induced lung tumor promotion and pulmonary inflammation in CXB mice. Carcinogenesis. 2002; 23(3):411-7. DOI: 10.1093/carcin/23.3.411. View

18.

Sparmann A, Bar-Sagi D . Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell. 2004; 6(5):447-58. DOI: 10.1016/j.ccr.2004.09.028. View

19.

Eberl G, Brawand P, MacDonald H . Selective bystander proliferation of memory CD4+ and CD8+ T cells upon NK T or T cell activation. J Immunol. 2000; 165(8):4305-11. DOI: 10.4049/jimmunol.165.8.4305. View

20.

Gungor N, Haegens A, Knaapen A, Godschalk R, Chiu R, Wouters E . Lung inflammation is associated with reduced pulmonary nucleotide excision repair in vivo. Mutagenesis. 2009; 25(1):77-82. DOI: 10.1093/mutage/gep049. View