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Plasticity of disseminating cancer cells in patients with epithelial malignancies

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Abstract

Current models suggest that at a certain but yet undefined time point of tumour development malignant cells with an aggressive phenotype start to disseminate via the blood stream into distant organs. This invasive phenotype appears to be associated with an epithelial–mesenchymal transition (EMT), which enables detachment of tumour cells from a primary site and migration. The reverse process of mesenchymal–epithelial transition (MET) might play a crucial role in the further steps of metastasis when circulating tumour cells (CTCs) settle down in distant organs and establish (micro-)metastasis. Nevertheless, the exact mechanisms and interplay of EMT and MET are only partially understood and their relevance in cancer patients is unclear. Research groups have just started to apply EMT-related markers in their studies on CTCs in cancer patients. In the present review, we summarize and discuss the current state of investigations on CTCs in the context of research on EMT/MET.

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Abbreviations

ALDH1:

adehyde dehydrogenase type 1

CK:

cytokeratin

CTC:

circulating tumour cell

DTC:

disseminated tumour cell

EGFR:

epidermal growth factor receptor

EMT:

epithelialmesenchymal transition

EpCAM:

epithelial cell adhesion molecule

IHC:

immunohistochemistry

MET:

mesenchymal–epithelial transition

MErT:

mesenchymalepithelial reverting transition

PCR:

polymerase chain reaction

RT-PCR:

reverse transcription polymerase chain reaction

TGF-beta:

transforming growth factor-beta

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Acknowledgements

This work was supported by grants from the Bundesministerium für Bildung und Forschung (K.P.), the European Research Council Advanced Investigator Grant No. ERC-2010-AdG_20100317 DISSECT (K.P.) The authors want to express their gratitude to Frauke Gotzheim for help in editing some parts of the manuscript.

Competing interests

KP has received research grants and speaker´s honoria from Veridex. CAP has received research grants and speaker’s honoraria from Veridex and Roche. NBK has no potential conflict of interest to declare.

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Bednarz-Knoll, N., Alix-Panabières, C. & Pantel, K. Plasticity of disseminating cancer cells in patients with epithelial malignancies. Cancer Metastasis Rev 31, 673–687 (2012). https://doi.org/10.1007/s10555-012-9370-z

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