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 epithelialmesenchymal 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 TM 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.
| Original language | English |
|---|---|
| Pages (from-to) | 449-455 |
| Number of pages | 7 |
| Journal | Breast Cancer Research and Treatment |
| Volume | 130 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Nov 2011 |
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Keywords
- Cancer stem cells
- Circulating tumor cells
- Cytokeratins
- Epithelial-mesenchymal transition
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Epithelial-mesenchymal transition and stemness features in circulating tumor cells from breast cancer patients. / Raimondi, Cristina; Gradilone, Angela; Naso, Giuseppe; Vincenzi, Bruno; Petracca, Arianna; Nicolazzo, Chiara; Palazzo, Antonella; Saltarelli, Rosa; Spremberg, Franco; Cortesi, Enrico; Gazzaniga, Paola.
In: Breast Cancer Research and Treatment, Vol. 130, No. 2, 11.2011, p. 449-455.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Epithelial-mesenchymal transition and stemness features in circulating tumor cells from breast cancer patients
AU - Raimondi, Cristina
AU - Gradilone, Angela
AU - Naso, Giuseppe
AU - Vincenzi, Bruno
AU - Petracca, Arianna
AU - Nicolazzo, Chiara
AU - Palazzo, Antonella
AU - Saltarelli, Rosa
AU - Spremberg, Franco
AU - Cortesi, Enrico
AU - Gazzaniga, Paola
PY - 2011/11
Y1 - 2011/11
N2 - 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 epithelialmesenchymal 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 TM 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.
AB - 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 epithelialmesenchymal 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 TM 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.
KW - Cancer stem cells
KW - Circulating tumor cells
KW - Cytokeratins
KW - Epithelial-mesenchymal transition
UR - http://www.scopus.com/inward/record.url?scp=82955187028&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=82955187028&partnerID=8YFLogxK
U2 - 10.1007/s10549-011-1373-x
DO - 10.1007/s10549-011-1373-x
M3 - Article
VL - 130
SP - 449
EP - 455
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
SN - 0167-6806
IS - 2
ER -