Bone metastasis in a novel breast cancer mouse model containing human breast and human bone
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In practice, investigations for bone metastasis of breast cancer rely heavily on models in vivo. Lacking of such ideal model makes it difficult to study the whole process or accurate mechanism of each step of this metastatic disease. Development of xenograft mouse models has made great contributions in this area. Currently, the best animal model of breast cancer metastasizing to bone is NOD/SCID-hu models containing human bone, which makes it possible to let the breast cancer cells and the bone target of osteotropic metastasis be both of human origin. We have developed a novel mouse model containing both human bone and breast, and proved it functional and reliable. In this study, a set of human breast cancer cell line including MDA-MB-231, MDA-MB-231BO, MCF-7, ZR-75-1 and SUM1315 were characterized their osteotropism in this model. A specific cell line SUM1315 made species-specific bone metastasis, certifying the osteotropism-identification utility of the novel mouse model. Furthermore, gene expression and microRNA expression profiling analysis were done to the two SUM1315 derived sub lines isolated and purified from the orthotopic and metastatic xenograft. In addition, to demonstrate the disparity between the “spontaneous” and “forced” bone metastasis in mouse model, MDA-MB-231 cells were inoculated into both the human implants in this model simultaneously, and then primary cultured and profiling analyzed. Supported by overall results of profiling analyses, this study suggested the novel model was a useful tool for understanding, preventing and treating bone metastasis of breast cancer, meanwhile it had provided significant information for further investigations.
KeywordsHuman microenvironment Bone metastasis Breast cancer Mouse model Expression profiling
We are grateful to Dr. Bei-Cheng Sun (Center of Liver Transplantation, the First Affiliated Hospital of Nanjing Medical University) for providing us with plenti-GFP lentivirus, to Stephen Ethier (University of Michigan) for providing us with SUM1315, to Dr. Jie Wang (Department of Medical Research, Guangzhou General Hospital of Guangzhou Command) for providing us with MDA-MB-231BO, and to Dr. Ji-Fu Wei (Clinical Experiment Center, the First Affiliated Hospital of Nanjing Medical University) for critical discussion in our study. This research was supported in part by the National Natural Science Foundation of China (81071753), the Six Kinds of Outstanding Talent Foundation of Jiangsu Province (06-B-069), and the Natural Science Foundation of Jiangsu Province (BK2008476, BK2009438 and BK2010581).
Conflict of interest
All the authors declared that they do not have any conflict of interest.
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