Optically imageable metastatic model of human breast cancer

Optically imageable metastatic model of human breast cancer
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DOI:
10.1023/a:1015510207431
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发表时间:
2002-01-01
影响因子:
4
通讯作者:
Hoffman, RM
Hoffman, RM
中科院分区:
医学3区
文献类型:
--
作者:
Li, XM;Wang, JW;Hoffman, RM

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我们报告了表达绿色荧光蛋白(GFP)的人乳腺癌MDA-MB-435的光学成像原位转移裸鼠模型。我们展示了活组织和完整动物中原发性和转移性生长的荧光成像。将表达 GFP 的肿瘤组织碎片缝合到右侧第二乳腺的口袋中。肿瘤组织发出强烈的荧光,从而能够在第 5 周对肿瘤生长进行全身成像。通过血管与荧光肿瘤的对比,原发性肿瘤的新血管形成也可以通过全身成像显现出来。尸检时,发现 MDA-MB-435-GFP 已转移至多个器官,包括 55% 动物的肺、15% 动物的淋巴结(包括腋窝淋巴结)和 10% 动物的肝脏。这些转移可以通过荧光成像在新鲜组织中显现出来。详细的荧光分析显示胸腔和淋巴系统的广泛转移。肺部的大转移结节涉及所有肺叶的大部分肺实质。淋巴结转移主要发生在腋窝部位。在肝脏中,在被膜下发现了荧光肉眼可见的转移结节。因此,该模型中的转移模式反映了临床转移性乳腺癌,并为该疾病的药物发现提供了强大的模型。
We report an optically imageable orthotopic metastatic nude mouse model of the human breast cancer MDA-MB-435 expressing green fluorescent protein (GFP). We demonstrate fluorescent imaging of primary and metastatic growth in live tissue and in intact animals. Fragments of tumor tissue expressing GFP were sutured into the pocket in the right second mammary gland. Tumor tissue was strongly fluorescent, enabling whole-body imaging of tumor growth by week 5. Neovascularization of the primary tumor was also visualized by whole-body imaging by contrast of the vessels to the fluorescent tumor. At autopsy, the MDA-MB-435-GFP was found to have metastasized to various organs, including the lung in 55% of the animals, the lymph nodes in 15% of the animals including axillary nodes, and the liver in 10% of the animals. These metastases could be visualized in fresh tissue by fluorescent imaging. Detailed fluorescence analysis visualized extensive metastasis in the thoracic cavity and the lymphatic system. Large metastatic nodules in the lung involved most of the pulmonary parenchyma in all lobes. Lymph node metastasis was found mainly in the axillary area. In the liver, fluorescent macroscopic metastatic nodules were found under the capsule. The metastatic pattern in the model thus reflected clinical metastatic breast cancer and provides a powerful model for drug discovery for this disease.