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Strain-specific variation in murine natural killer gene complex contributes to differences in immunosurveillance for urethane-induced lung cancer. Cancer Res 2012 Sep 01;72(17):4311-7 PMID: 22751136 PMCID: PMC3432713

Pubmed ID

22751136

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide and results from a complex interaction between carcinogen exposure and inherent susceptibility. Despite its prevalence, genetic factors that predispose to the development of lung cancer remain elusive. Inbred mouse models offer a unique and clinically relevant tool to study genetic factors that contribute to lung carcinogenesis due to the development of tumors that resemble human adenocarcinoma and broad strain-specific variation in cancer incidence after carcinogen administration. Here, we set out to investigate whether strain-specific variability in tumor immunosurveillance contributes to differences in lung cancer. Using bone marrow transplantation, we determined that hematopoietic cells from lung cancer-resistant mice could significantly impede the development of cancer in a susceptible strain. Furthermore, we show that this is not due to differences in tumor-promoting inflammatory changes or variability in immunosurveillance by the adaptive immune system but results from strain-specific differences in natural killer (NK) cell cytotoxicity. Using a newly discovered congenic strain of mice, we show a previously unrecognized role for strain-specific polymorphisms in the natural killer gene complex (NKC) in immunosurveillance for carcinogen-induced lung cancer. Because polymorphisms in the NKC are highly prevalent in man, our data may explain why certain individuals without obvious risk factors develop lung cancer whereas others remain resistant to the disease despite heavy environmental carcinogen exposure.

Author List

Kreisel D, Gelman AE, Higashikubo R, Lin X, Vikis HG, White JM, Toth KA, Deshpande C, Carreno BM, You M, Taffner SM, Yokoyama WM, Bui JD, Schreiber RD, Krupnick AS

Author

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




Scopus

2-s2.0-84865794098   15 Citations

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

Adaptive Immunity
Animals
Bone Marrow Cells
Carcinogens
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Chromosomes
Humans
Immunity, Innate
Immunologic Surveillance
Inflammation
Killer Cells, Natural
Lung Neoplasms
Male
Mice
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Knockout
Polymorphism, Genetic
Species Specificity
Urethane
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e