title: Bone metastasis in a novel breast cancer mouse model containing human breast and human bone.
abstract: 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.
authors.affiliation: Department of Breast Surgery, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
authors.forename: Tian-Song
authors.initials: TS
authors.lastname: Xia
authors.forename: Guo-Zhu
authors.initials: GZ
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.forename: Xiao-An
authors.initials: XA
authors.lastname: Liu
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Zhou
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Zhang
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Zha
authors.forename: Qing
authors.initials: Q
authors.lastname: Du
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Ni
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.forename: Su-Yu
authors.initials: SY
authors.lastname: Miao
authors.forename: Shui
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D005260:Female; D005270:Femur Head / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006085:Graft Survival; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D014162:Transfection; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment
chemical_list: D035683:MicroRNAs; D049452:Green Fluorescent Proteins