Circulating Tumor Cells as a Window on Metastasis Biology in Lung Cancer
Circulating Tumor Cells as a Window on Metastasis Biology in Lung Cancer
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DOI：
10.1016/j.ajpath.2010.12.003
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发表时间：
2011-03-01
影响因子：
6
通讯作者：
Dive, Caroline
中科院分区：
文献类型：
--
作者：
Hou, Jian-Mei;Krebs, Matthew;Dive, Caroline
转移性癌症患者循环小细胞(CTC)数量的变化与上皮细胞向间充质细胞转化(EMT)的特征--黏附丧失--增强的细胞迁移和侵袭相一致。肿瘤细胞也通过维持细胞间接触的集体迁移进行侵袭，与此相一致的是在转移性癌症患者中观察到的循环肿瘤微栓子(CTM；连续的肿瘤细胞群)。我们采用血液滤过的方法，检测了肺癌组织中细胞角蛋白、E-钙粘蛋白、波形蛋白、神经钙粘蛋白的标志物和细胞凋亡的发生率，以探讨肺癌患者侵袭的可能机制(S)，并验证了肿瘤细胞具有生存优势的假说。住院期间和。观察到CTC和CTM中EMT标记物的患者间异质性。波形蛋白仅在部分CTC中表达，但在CTM内的大部分细胞中表达；E-钙粘蛋白在CTM中表达缺失，呈胞浆或胞核表达，极少在CTM的细胞表面表达。CTC亚群出现凋亡，但CTM内未见细胞凋亡。这项初步研究表明，EMT在肺癌患者循环内的肿瘤细胞中不是均匀进行的，CTM内细胞的集体迁移和增强的生存可能有助于肺癌的转移。对CTCS/CTM中的转移潜能和EMT的多重分析和进一步详细的探索现在在更大的患者队列中是有必要的。(Am J Pathol 2011,178：989-996.Doi：10.1016/j.ajpath.2010.12.003)
Circulating minor cell (CTC) number in metastatic cancer patients yields prognostic information consistent with enhanced cell migration and invasion via loss of adhesion, a feature of epithelial-to-mesenchymal transition (EMT). Tumor cells also invade via collective migration with maintained cell-cell contacts and consistent with this is the circulating tumor microemboli (CTM; contiguous groups of tumor cells) that are observed in metastatic cancer patients. Using a blood filtration approach, we examined markers of EMT (cytokeratins, E-cadherin, vimentin, neural cadherin) and prevalence of apoptosis in CTCs and CTM to explore likely mechanism(s) of invasion in lung cancer patients and address the hypothesis that cells within CTM have a survival advantage. Intra-patient and. inter-patient heterogeneity was observed for EMT markers in CTCs and CTM. Vimentin was only expressed in some CTCs, but in the majority of cells within CTM; E-cadherin expression was lost, cytoplasmic or nuclear, and rarely expressed at the surface of the cells within CTM. A subpopulation of CTCs was apoptotic, but apoptosis was absent within CTM. This pilot study suggests that EMT is not prosecuted homogeneously in tumor cells within the circulation of lung cancer patients and that collective migration and enhanced survival of cells within CTM might contribute to lung cancer metastasis. Multiplex analysis and further detailed exploration of metastatic potential and EMT in CTCs/CTM is now warranted in a larger patient cohort. (Am J Pathol 2011, 178:989-996. DOI: 10.1016/j.ajpath.2010.12.003)