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

Objective: 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.

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 (10(1)-10(5) 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 10(4) 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 10(3) 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 10(3) 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.

Conclusions: NSG mice may be the most suitable strain for testing tumorigenicity of lung cancer, especially if only a few cells are available.