Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH, Heidelberg, Germany.
Nat Biotechnol. 2013 Jun;31(6):539-44. doi: 10.1038/nbt.2576. Epub 2013 Apr 21.
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.
人们假设癌转移是由患者血液中存在的循环肿瘤细胞（CTC）亚群引发的。然而，尽管 CTC 的存在是几种癌实体预后不良的指标，但 CTC 中是否存在并表型转移起始细胞（MIC）尚未得到实验证明。在这里，我们开发了异种移植测定法，并使用该方法证明原发性人腔乳腺癌 CTC 中含有 MIC，这些 MIC 可在小鼠中引发骨、肺和肝转移。这些含有 MIC 的 CTC 群体表达 EPCAM、CD44、CD47 和 MET。在一小部分有转移的患者中，EPCAM(+)CD44(+)CD47(+)MET(+)CTC 的数量，但不是大块 EPCAM(+)CTC 的数量，与总生存率降低和转移部位数量增加相关。这些数据描述了功能循环 MIC 和相关标记物，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。
