A mouse mode of human breast cancer metastasis to human bone
A mouse mode of human breast cancer metastasis to human bone
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DOI：
10.1158/0008-5472.can-04-1408
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发表时间：
2005-07-15
期刊：
影响因子：
11.2
通讯作者：
Rosenblatt, M
中科院分区：
文献类型：
--
作者：
Kuperwasser, C;Dessain, S;Rosenblatt, M
目前，人类乳腺癌从原位部位转移到骨骼的体内模型不存在，因此很难研究骨骼转移的许多步骤。此外，用于识别乳腺癌转移到骨骼的机制的模型仅限于心内注射，后者将癌细胞直接播种到循环中，从而绕过转移过程中的早期步骤。这样的模型不能反映患者发生的转移的完整过程。我们已经开发了一种乳腺癌转移的动物模型，其中乳腺癌细胞和骨质性转移的骨骼靶标都是人类的起源。植入的人骨具有功能性，基于在小鼠血液中找到人IgG，小鼠脾脏中的人类B细胞和正常的骨组织学。此外，特定人类乳腺癌细胞系的原位注射SUM1315（源自患者的转移性结节），后来导致骨转移和肺转移。就骨骼而言，转移是对人植入物而不是小鼠骨骼的，表明物种特异性的骨骼动物。该模型复制了在乳腺癌骨骼转移患者中观察到的事件，并作为研究该疾病的有用且相关的模型。
Currently, an in vivo model of human breast cancer metastasizing from the orthotopic site to bone does not exist, making it difficult to study the many steps of skeletal metastasis. Moreover, models used to identify the mechanisms by which breast cancer metastasizes to bone are limited to intracardiac injection, which seeds the cancer cells directly into the circulation, thus bypassing the early steps in the metastatic process. Such models do not reflect the full process of metastasis occurring in patients. We have developed an animal model of breast cancer metastasis in which the breast cancer cells and the bone target of osteotropic metastasis are both of human origin. The engrafted human bone is functional, based on finding human IgG in the mouse bloodstream, human B cells in the mouse spleen, and normal bone histology. Furthermore, orthotopic injection of a specific human breast cancer cell line, SUM1315 (derived from a metastatic nodule in a patient), later resulted in both bone and lung metastases. In the case of bone, metastasis was to the human implant and not the mouse skeleton, indicating a species-specific osteotropism. This model replicates the events observed in patients with breast cancer skeletal metastases and serves as a useful and relevant model for studying the disease.