Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors
Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors
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DOI：
10.1172/jci200522320
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发表时间：
2005-01-01
影响因子：
15.9
通讯作者：
Massagué, J
中科院分区：
文献类型：
--
作者：
Minn, AJ;Kang, YB;Massagué, J
我们使用生物发光成像来揭示免疫缺陷小鼠中人乳腺癌细胞转移形成的模式。来自乳腺癌患者胸腔积液培养物中建立的群体的单个细胞显示出不同的器官特异性转移模式。来自这个群体的单细胞后代表现出明显不同的能力转移到骨，肺，或肾上腺髓质。这表明转移到不同器官有不同的要求。转录组学分析显示，这些不同的单细胞后代类似地表达先前描述的“预后不良”基因表达特征。使用转录组学数据集的无监督分类支持这样的假设，即乳腺癌细胞的器官特异性转移是由转移特异性基因控制的，这些基因与一般预后不良的基因表达特征是分开的。此外，通过使用与这些细胞转移到骨的能力相关的基因表达特征，我们能够区分优先转移到骨的原发性乳腺癌和优先转移到其他地方的原发性乳腺癌。这些结果表明，在小鼠模型中鉴定的骨特异性转移表型和基因表达特征可能具有临床相关性。
We used bioluminescence imaging to reveal patterns of metastasis formation by human breast cancer cells in immunodeficient mice. Individual cells from a population established in culture from the pleural effusion of a breast cancer patient showed distinct patterns of organ-specific metastasis. Single-cell progenies derived from this population exhibited markedly different abilities to metastasize to the bone, lung, or adrenal medulla. which suggests that metastases to different organs have different requirements. Transcriptomic profiling revealed that these different single-cell progenies similarly express a previously described "poor-prognosis" gene expression signature. Unsupervised classification using the transcriptomic data set supported the hypothesis that organ-specific metastasis by breast cancer cells is controlled by metastasis-specific genes that are separate from a general poor-prognosis gene expression signature. Furthermore, by using a gene expression signature associated with the ability of these cells to metastasize to bone, we were able to distinguish primary breast carcinomas that preferentially metastasized to bone from those that preferentially metastasized elsewhere. These results suggest that the bone-specific metastatic phenotypes and gene expression signature identified in a mouse model may be clinically relevant.