Characterization of a Novel Mouse Model of Spontaneous Human Lung Cancer Metastasis

To identify new strategies against lung metastasis and understand the underlying mechanisms, a highly metastatic pulmonary large cell carcinoma cell line model (801BL) was established through two rounds of in vivo selection using a nude mouse xenograft model. Satellite tandem repeat (STR) analysis confirmed the same genomic background of the newly established metastatic cell line 801BL as the non-metastatic 801C and low-metastatic 801D counterparts. Our study showed that 100% of mice (8 out of 8) injected subcutaneously with 801BL cells developed lung metastatic tumors, while none of the mice injected with 801C cells had lung metastasis (p<0.0001). Highly metastatic 801BL cells showed alterations in morphology and invasion capability when compared with 801C and/or 801D cell lines A comparative proteomic analysis between 801BL and 801C followed by bioinformatics analysis revealed significant alterations in several dominant cell signalling networks in the highly metastatic cell line. Western blot confirmed the proteomic findings for several proteins from each signalling network. Since the highly metastatic cell line and its non-metastatic counterpart share the identical genetic background, this model provides a powerful tool for study of the mechanisms underlying lung cancer metastasis.