Abstract
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.
Highlights
Lung cancer is the deadliest type of cancer for both men and women
It is estimated that 234,030 new cases of lung cancer will be diagnosed in 2018 and 154,050 deaths are projected in the United States, where 90% of cancer deaths can be attributed to metastasis [1, 2]
A PCR-based satellite tandem repeat (STR) analysis confirmed that the genomic background of the newly established metastatic cell line 801BL was the same as that of the non-metastatic counterpart 801C and low-metastatic counterpart 801D (Table 1)
Summary
Lung cancer is the deadliest type of cancer for both men and women. It is estimated that 234,030 new cases of lung cancer will be diagnosed in 2018 and 154,050 deaths are projected in the United States, where 90% of cancer deaths can be attributed to metastasis [1, 2]. The underlying mechanisms of metastasis in most cancers including lung cancer are still poorly understood. Metastasis studies require both pathologic and in vivo animal analyses, because metastasis is a biological process with multiple steps that can only be described based on in vivo analysis. Several types of animal models have been developed for experimental lung cancer research including chemically induced lung tumors, human tumor xenografts, and transgenic mouse models [4]. Among these models, xenografts are reliable tools for the study of metastatic disease mainly because other models generally produce a low incidence of distant metastatic disease [5]
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