title: Epithelial-mesenchymal transition and stemness features in circulating tumor cells from breast cancer patients.
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.
authors.affiliation: Division of Medical Oncology, Sapienza University of Rome, Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Raimondi
authors.forename: Angela
authors.initials: A
authors.lastname: Gradilone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Naso
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Arianna
authors.initials: A
authors.lastname: Petracca
authors.forename: Chiara
authors.initials: C
authors.lastname: Nicolazzo
authors.forename: Antonella
authors.initials: A
authors.lastname: Palazzo
authors.forename: Rosa
authors.initials: R
authors.lastname: Saltarelli
authors.forename: Franco
authors.initials: F
authors.lastname: Spremberg
authors.forename: Enrico
authors.initials: E
authors.lastname: Cortesi
authors.forename: Paola
authors.initials: P
authors.lastname: Gazzaniga
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D005353:Fibronectins; D007527:Isoenzymes; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D050697:Retinal Dehydrogenase; D014746:Vimentin; C506487:ESR1 protein, human; C510223:ALDH1A1 protein, human; C508053:ERBB2 protein, human