Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay
Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay
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DOI：
10.1038/nbt.2576
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发表时间：
2013-06-01
影响因子：
46.9
通讯作者：
Trumpp, Andreas
中科院分区：
文献类型：
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作者：
Baccelli, Irene;Schneeweiss, Andreas;Trumpp, Andreas
据推测，癌症转移是由患者血液中发现的循环肿瘤细胞(CTCs)亚群启动的。然而，尽管CTCs的存在是一些肿瘤预后不良的指标，但CTCs中转移起始细胞(MIC)的存在和表型尚未得到实验证明。在这里，我们开发了一种异种移植试验，并用它来表明原发的人类管腔乳腺癌CTCs含有MIC，可以引起小鼠的骨、肺和肝转移。这些含MIC的CTC群体表达EPCAM、CD44、CD47和MET。在一小部分转移患者中，EPCAM(+)CD44(+)CD47(+)Met(+)CTCs的数量，而不是大量EpCAM(+)CTCs的数量，与较低的总生存率和较多的转移灶有关。这些数据描述了功能循环的MIC和相关的标志物，这可能有助于设计更好的工具来诊断和治疗转移性乳腺癌。
It has been hypothesized that carcinoma metastasis is initiated by a subpopulation of circulating tumor cells (CTCs) found in the blood of patients. However, although the presence of CTCs is an indicator of poor prognosis in several carcinoma entities, the existence and phenotype of metastasis-initiating cells (MICs) among CTCs has not been experimentally demonstrated. Here we developed a xenograft assay and used it to show that primary human luminal breast cancer CTCs contain MICs that give rise to bone, lung and liver metastases in mice. These MIC-containing CTC populations expressed EPCAM, CD44, CD47 and MET. In a small cohort of patients with metastases, the number of EPCAM(+)CD44(+)CD47(+)MET(+) CTCs, but not of bulk EPCAM(+) CTCs, correlated with lower overall survival and increased number of metastasic sites. These data describe functional circulating MICs and associated markers, which may aid the design of better tools to diagnose and treat metastatic breast cancer.