期刊论文详细信息
BMC Cancer
Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition
Research Article
Tobias M Gorges1  Michael Drosch1  Thomas M Zollner1  Lars Röse1  Thomas Krahn1  Oliver von Ahsen2  Ingeborg Tinhofer3 
[1] Bayer Pharma AG, Muellerstr. 178, 13353, Berlin, Germany;Bayer Pharma AG, Muellerstr. 178, 13353, Berlin, Germany;Boehringer Ingelheim Pharma GmbH & Co. KG Drug Metabolism&Pharmacokinetics, Biberach, Germany;Charite CCM, Klinik für Radioonkologie und Strahlentherapie Chariteplatz 1, 10117, Berlin, Germany;
关键词: Circulating tumour cells;    Breast cancer;    Xenograft;    Metastasis;    Epithelial-mesenchymal transition;   
DOI  :  10.1186/1471-2407-12-178
 received in 2012-01-23, accepted in 2012-04-11,  发布年份 2012
来源: Springer
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【 摘 要 】

BackgroundCirculating tumour cells (CTCs) have shown prognostic relevance in metastatic breast, prostate, colon and pancreatic cancer. For further development of CTCs as a biomarker, we compared the performance of different protocols for CTC detection in murine breast cancer xenograft models (MDA-MB-231, MDA-MB-468 and KPL-4). Blood samples were taken from tumour bearing animals (20 to 200 mm2) and analysed for CTCs using 1. an epithelial marker based enrichment method (AdnaTest), 2. an antibody independent technique, targeting human gene transcripts (qualitative PCR), and 3. an antibody-independent approach, targeting human DNA-sequences (quantitative PCR). Further, gene expression changes associated with epithelial-to-mesenchymal transition (EMT) were determined with an EMT-specific PCR assay.MethodsWe used the commercially available Adna Test, RT-PCR on human housekeeping genes and a PCR on AluJ sequences to detect CTCs in xenografts models. Phenotypic changes in CTCs were tested with the commercially available “Human Epithelial to Mesenchymal Transition RT-Profiler PCR Array”.ResultsAlthough the AdnaTest detects as few as 1 tumour cell in 1 ml of mouse blood spiking experiments, no CTCs were detectable with this approach in vivo despite visible metastasis formation. The presence of CTCs could, however, be demonstrated by PCR targeting human transcripts or DNA-sequences - without epithelial pre-enrichment. The failure of CTC detection by the AdnaTest resulted from downregulation of EpCAM, whereas mesenchymal markers like Twist and EGFR were upregulated on CTCs. Such a change in the expression profile during metastatic spread of tumour cells has already been reported and was linked to a biological program termed epithelial-mesenchymal transition (EMT).ConclusionsThe use of EpCAM-based enrichment techniques leads to the failure to detect CTC populations that have undergone EMT. Our findings may explain clinical results where low CTC numbers have been reported even in patients with late metastatic cancers. These results are a starting point for the identification of new markers for detection or capture of CTCs, including the mesenchymal-like subpopulations.

【 授权许可】

Unknown   
© Gorges et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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