Bone metastasis in a novel breast cancer mouse model containing human breast and human bone
Bone metastasis in a novel breast cancer mouse model containing human breast and human bone
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DOI：
10.1007/s10549-011-1496-0
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发表时间：
2012-04-01
影响因子：
3.8
通讯作者：
Wang, Shui
中科院分区：
文献类型：
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作者：
Xia, Tian-Song;Wang, Guo-Zhu;Wang, Shui
在实践中，乳腺癌骨转移的研究在很大程度上依赖于体内模型。由于缺乏理想的动物模型，很难研究这种转移性疾病的整个过程或每一步的确切机制。异种移植小鼠模型的建立为这一领域的研究做出了巨大贡献。目前，最好的乳腺癌骨转移动物模型是含有人骨的NOD/SCID-hu模型，这使得乳腺癌细胞和骨转移靶点都是人源性的成为可能。我们已经开发了一种新的小鼠模型，包含人骨和乳房，并证明它的功能和可靠。本研究以人乳腺癌细胞株MDA-MB-231、MDA-MB-231 BO、MCF-7、ZR-75-1和SUM 1315为研究对象，在此模型中研究了它们的趋骨性。一个特定的细胞系SUM 1315产生了种属特异性骨转移，证明了新的小鼠模型的向骨性鉴定效用。此外，对从原位和转移性异种移植物分离和纯化的两个SUM 1315衍生的亚系进行基因表达和microRNA表达谱分析。此外，为了证明小鼠模型中“自发”和“强制”骨转移之间的差异，将MDA-MB-231细胞同时接种到该模型中的两个人植入物中，然后进行原代培养和谱分析。本研究结果表明，该模型为乳腺癌骨转移的研究、预防和治疗提供了一个有效的工具，同时也为进一步研究乳腺癌骨转移提供了重要信息。
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.