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Epithelial-mesenchymal transition and stemness features in circulating tumor cells from breast cancer patients

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Abstract

Currently used methods to detect and enumerate circulating tumor cells (CTCs) rely on the expression of the epithelial cell adhesion molecule (EpCAM) and cytokeratins. This selection may exclude cells that have undergone intrinsic modifications of their phenotype, as epithelial-mesenchymal transition (EMT). Aim of the study was to investigate the expression of EMT and stemness markers in CTCs from breast cancer patients in all stages of disease. 92 female breast cancer patients were enrolled. CTCs were isolated by CELLection™ Dynabeads® coated with the monoclonal antibody toward EpCam. Samples found positive for CTCs presence (CD45−/CK+) were evaluated for the expression of ER alpha, HER2, ALDH1, vimentin, and fibronectin. Samples negative for CTCs presence (CD45−/CK−) were also evaluated for the expression of vimentin and fibronectin, used as markers of EMT. CTCs were found in 66% of patients. The distribution of CTCs presence according to stage and grade of disease was found statistically significant. The expression of ALDH1 on CTCs was found to correlate to stage of disease and to the expression of vimentin and fibronectin. In 34% of patients, we detected cells with negative CK/CD45 expression but positive expression of vimentin and fibronectin. There is an urgent need for optimizing CTCs detection methods through the inclusion of EMT markers. The detection of cells in mesenchymal transition, retaining EMT and stemness features, may contribute to discover additional therapeutic targets useful to eradicate micrometastatic disease in breast cancer.

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Acknowledgments

This study was partially supported by Ar.ger.On onlus and F.O.RO. onlus.

Conflict of Interest

All authors declare no conflict of interest.

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Authors and Affiliations

  1. Division of Medical Oncology, Sapienza University of Rome, Rome, Italy

    Cristina Raimondi, Giuseppe Naso, Antonella Palazzo & Enrico Cortesi

  2. Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy

    Angela Gradilone, Arianna Petracca, Chiara Nicolazzo & Paola Gazzaniga

  3. Division of Medical Oncology, Campus Biomedico University of Rome, Rome, Italy

    Bruno Vincenzi

  4. Division of Medical Oncology, Hospital “S. Giovanni Evangelista”, Tivoli, Rome, Italy

    Rosa Saltarelli & Franco Spremberg

Authors
  1. Cristina Raimondi
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  2. Angela Gradilone
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  3. Giuseppe Naso
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  4. Bruno Vincenzi
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  5. Arianna Petracca
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  6. Chiara Nicolazzo
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  7. Antonella Palazzo
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  8. Rosa Saltarelli
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  9. Franco Spremberg
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  10. Enrico Cortesi
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  11. Paola Gazzaniga
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Corresponding author

Correspondence to Paola Gazzaniga.

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Raimondi, C., Gradilone, A., Naso, G. et al. Epithelial-mesenchymal transition and stemness features in circulating tumor cells from breast cancer patients. Breast Cancer Res Treat 130, 449–455 (2011). https://doi.org/10.1007/s10549-011-1373-x

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  • DOI: https://doi.org/10.1007/s10549-011-1373-x

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