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Cancer and Metastasis Reviews

, Volume 31, Issue 3–4, pp 673–687 | Cite as

Plasticity of disseminating cancer cells in patients with epithelial malignancies

  • Natalia Bednarz-Knoll
  • Catherine Alix-Panabières
  • Klaus Pantel
Article

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.

Keywords

Cancer progression CTC Dissemination Metastasis EMT MET Cell plasticity 

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

Notes

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.

Authors’ contributions

All authors contributed to the writing of the manuscript.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Natalia Bednarz-Knoll
    • 1
  • Catherine Alix-Panabières
    • 2
    • 3
    • 4
  • Klaus Pantel
    • 1
  1. 1.Department of Tumour Biology, Center of Experimental Medicine, University Cancer Center HamburgUniversity Medical Centre Hamburg-EppendorfHamburgGermany
  2. 2.Institute of Research in Biotherapy, Laboratory of Rare Human Circulating CellsUniversity Medical CentreMontpellierFrance
  3. 3.Laboratory of Cell and Hormonal Biology, Arnaud de Villeneuve HospitalUniversity Medical CentreMontpellierFrance
  4. 4.Biostatistics and Public HealthUniversity Institute of Clinical Research UM1-EA2415-EpidemiologyMontpellierFrance

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