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Open AccessArticle

Spectrum of Epithelial-Mesenchymal Transition Phenotypes in Circulating Tumour Cells from Early Breast Cancer Patients

1
Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology of the University of Gdansk and Medical University of Gdansk, 80-211 Gdańsk, Poland
2
Department of Surgical Oncology, Medical University of Gdansk, 80-210 Gdańsk, Poland
3
Department of Medical Laboratory Diagnostics-Biobank, Medical University of Gdansk, 80-210 Gdańsk, Poland
4
Biobanking and Biomolecular Resources Research Infrastructure (BBMRI.PL), 80-210 Gdansk, Poland
5
Department of Clinical Science, University of Bergen, 5007 Bergen, Norway
6
Department of Oncology and Radiotherapy, Medical University of Gdansk, 80-210 Gdańsk, Poland
*
Authors to whom correspondence should be addressed.
Authors share equal contribution to this work.
Cancers 2019, 11(1), 59; https://doi.org/10.3390/cancers11010059
Received: 12 December 2018 / Revised: 30 December 2018 / Accepted: 2 January 2019 / Published: 9 January 2019
(This article belongs to the Special Issue Circulating Tumor Cells (CTCs))
Circulating tumour cells (CTCs) can provide valuable prognostic information in a number of epithelial cancers. However, their detection is hampered due to their molecular heterogeneity, which can be induced by the epithelial-mesenchymal transition (EMT) process. Therefore, current knowledge about CTCs from clinical samples is often limited due to an inability to isolate wide spectrum of CTCs phenotypes. In the current work, we aimed at isolation and molecular characterization of CTCs with different EMT status in order to establish their clinical significance in early breast cancer patients. We have obtained CTCs-enriched blood fraction from 83 breast cancer patients in which we have tested the expression of epithelial, mesenchymal and general breast cancer CTCs markers (MGB1/HER2/CK19/CDH1/CDH2/VIM/PLS3), cancer stem cell markers (CD44, NANOG, ALDH1, OCT-4, CD133) and cluster formation gene (plakoglobin). We have shown that in the CTCs-positive patients, epithelial, epithelial-mesenchymal and mesenchymal CTCs markers were detected at a similar rate (in 28%, 24% and 24%, respectively). Mesenchymal CTCs were characterized by the most aggressive phenotype (significantly higher expression of CXCR4, uPAR, CD44, NANOG, p < 0.05 for all), presence of lymph node metastases (p = 0.043), larger tumour size (p = 0.023) and 7.33 higher risk of death in the multivariate analysis (95% CI 1.06–50.41, p = 0.04). Epithelial-mesenchymal subtype, believed to correspond to highly plastic and aggressive state, did not show significant impact on survival. Gene expression profile of samples with epithelial-mesenchymal CTCs group resembled pure epithelial or pure mesenchymal phenotypes, possibly underlining degree of EMT activation in particular patient’s sample. Molecular profiling of CTCs EMT phenotype provides more detailed and clinically informative results, proving the role of EMT in malignant cancer progression in early breast cancer. View Full-Text
Keywords: circulating tumour cells; epithelial-mesenchymal transition; cancer stem cell markers; breast cancer; prognostic factor circulating tumour cells; epithelial-mesenchymal transition; cancer stem cell markers; breast cancer; prognostic factor
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MDPI and ACS Style

Markiewicz, A.; Topa, J.; Nagel, A.; Skokowski, J.; Seroczynska, B.; Stokowy, T.; Welnicka-Jaskiewicz, M.; Zaczek, A.J. Spectrum of Epithelial-Mesenchymal Transition Phenotypes in Circulating Tumour Cells from Early Breast Cancer Patients. Cancers 2019, 11, 59.

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