Higher susceptibility of NOD/LtSz-scid Il2rg-/- NSG mice to xenotransplanted lung cancer cell lines

Abstract

Nobuhiro Kanaji,1 Akira Tadokoro,1 Kentaro Susaki,1 Saki Yokokura,1 Kiyomi Ohmichi,2 Reiji Haba,2 Naoki Watanabe,1 Shuji Bandoh,1 Tomoya Ishii,1 Hiroaki Dobashi,1 Takuya Matsunaga11Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan; 2Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, JapanPurpose: No lung cancer xenograft model using non-obese diabetic (NOD)-scid Il2rg-/- mice has been reported. The purpose of this study is to select a suitable mouse strain as a xenogenic host for testing tumorigenicity of lung cancer.Materials and methods: We directly compared the susceptibility of four immunodeficient mouse strains, c-nu, C.B-17 scid, NOD-scid, and NOD/LtSz-scid Il2rg-/- (NSG) mice, for tumor formation from xenotransplanted lung cancer cell lines. Various numbers (101–105 cells/head) of two lung cancer cell lines, A549 and EBC1, were subcutaneously inoculated and tumor sizes were measured every week up to 12 weeks.Results: When 104 EBC1 cells were inoculated, no tumor formation was observed in BALB/c-nu or C.B-17 scid mice. Tumors developed in two of the five NOD-scid mice (40%) and in all the five NSG mice (100%). When 103 EBC1 cells were injected, no tumors developed in any strain other than NSG mice, while tumorigenesis was achieved in all the five NSG mice (100%, P=0.0079) within 9 weeks. NSG mice similarly showed higher susceptibility to xenotransplantation of A549 cells. Tumor formation was observed only in NSG mice after inoculation of 103 or fewer A549 cells (40% vs 0% in 15 NSG mice compared with others, respectively, P=0.0169). We confirmed that the engrafted tumors originated from inoculated human lung cancer cells by immunohistochemical staining with human cytokeratin and vimentin.Conclusion: NSG mice may be the most suitable strain for testing tumorigenicity of lung cancer, especially if only a few cells are available.Keywords: NOD-scid Il2rg(null), tumorigenicity, xenotransplantation, xenograft, mouse model