title: Thyrospheres From Normal or Malignant Thyroid Tissue Have Different Biological, Functional, and Genetic Features.
abstract: BACKGROUND
  Cancer stem cells from several human malignancies, including poorly differentiated thyroid carcinoma and thyroid cancer cell lines, have been cultured in vitro as sphere-forming cells. These thyroid cancer stem cells were proven to be able to reproduce the original tumor in a xenograft orthotopic model.
  
  
  OBJECTIVE
  The objective of the study was to characterize papillary thyroid carcinoma (PTC) spheres from well-differentiated thyroid cancer and normal thyroid (NT) spheres obtained from the contralateral thyroid tissue of the same patient.
  
  
  METHODS
  Thyrospheres from PTCs and NTs were isolated.
  
  
  METHODS
  Gene expression analysis by real-time PCR, immunofluorescence studies, and fluorescence-activated cell sorter analysis in thyrospheres from PTCs and NTs have been evaluated.
  
  
  CONCLUSIONS
  Compared with NT spheres, PTC spheres are larger, more irregular, and more clonogenic and have a higher rate of symmetric division. Moreover, PTC spheres express higher levels of stem cell markers and lower levels of thyroid-specific genes compared with NT spheres. Under appropriate conditions, NT spheres differentiated into thyrocytes, whereas PTC spheres did not, displaying a defect in the differentiation potential. Immunofluorescence experiments indicated that, in NT spheres, progenitor cells are mainly present in the sphere core, and the sphere periphery contains thyroid precursor cells already committed to differentiation. PTC spheres are not polarized like NT spheres. Unlike cells differentiated from NT spheres, TSH did not significantly stimulate cAMP production in cells differentiated from PTC spheres. A microarray analysis performed in paired samples (NT and PTC spheres from the same patient) indicated that NT and PTC spheres display a gene expression pattern typical of stem/progenitor cells; however, compared with NT spheres, PTC spheres display a unique gene expression pattern that might be involved in PTC progression.
authors.affiliation: Department of Clinical and Molecular Bio-Medicine (F.G., V.V., M.L.N., S.L., R.V., F.F.), Endocrinology Unit, Garibaldi-Nesima Medical Center, University of Catania, 95122 Catania, Italy; Immunology and Pharmacotherapy Area (A.F.), Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00165 Rome, Italy; Department of Motor Sciences (V.V.), School of Human and Social Sciences, "Kore" University of Enna, 94100 Enna, Italy; Division of Endocrinology (R.M., A.B.), Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; and HUMANITAS (R.V.), Catania Oncology Center, 95126 Catania, Italy.
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Gianì
authors.affiliation: Department of Clinical and Molecular Bio-Medicine (F.G., V.V., M.L.N., S.L., R.V., F.F.), Endocrinology Unit, Garibaldi-Nesima Medical Center, University of Catania, 95122 Catania, Italy; Immunology and Pharmacotherapy Area (A.F.), Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00165 Rome, Italy; Department of Motor Sciences (V.V.), School of Human and Social Sciences, "Kore" University of Enna, 94100 Enna, Italy; Division of Endocrinology (R.M., A.B.), Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; and HUMANITAS (R.V.), Catania Oncology Center, 95126 Catania, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Vella
authors.affiliation: Department of Clinical and Molecular Bio-Medicine (F.G., V.V., M.L.N., S.L., R.V., F.F.), Endocrinology Unit, Garibaldi-Nesima Medical Center, University of Catania, 95122 Catania, Italy; Immunology and Pharmacotherapy Area (A.F.), Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00165 Rome, Italy; Department of Motor Sciences (V.V.), School of Human and Social Sciences, "Kore" University of Enna, 94100 Enna, Italy; Division of Endocrinology (R.M., A.B.), Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; and HUMANITAS (R.V.), Catania Oncology Center, 95126 Catania, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Nicolosi
authors.affiliation: Department of Clinical and Molecular Bio-Medicine (F.G., V.V., M.L.N., S.L., R.V., F.F.), Endocrinology Unit, Garibaldi-Nesima Medical Center, University of Catania, 95122 Catania, Italy; Immunology and Pharmacotherapy Area (A.F.), Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00165 Rome, Italy; Department of Motor Sciences (V.V.), School of Human and Social Sciences, "Kore" University of Enna, 94100 Enna, Italy; Division of Endocrinology (R.M., A.B.), Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; and HUMANITAS (R.V.), Catania Oncology Center, 95126 Catania, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fierabracci
authors.affiliation: Department of Clinical and Molecular Bio-Medicine (F.G., V.V., M.L.N., S.L., R.V., F.F.), Endocrinology Unit, Garibaldi-Nesima Medical Center, University of Catania, 95122 Catania, Italy; Immunology and Pharmacotherapy Area (A.F.), Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00165 Rome, Italy; Department of Motor Sciences (V.V.), School of Human and Social Sciences, "Kore" University of Enna, 94100 Enna, Italy; Division of Endocrinology (R.M., A.B.), Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; and HUMANITAS (R.V.), Catania Oncology Center, 95126 Catania, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Lotta
authors.affiliation: Department of Clinical and Molecular Bio-Medicine (F.G., V.V., M.L.N., S.L., R.V., F.F.), Endocrinology Unit, Garibaldi-Nesima Medical Center, University of Catania, 95122 Catania, Italy; Immunology and Pharmacotherapy Area (A.F.), Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00165 Rome, Italy; Department of Motor Sciences (V.V.), School of Human and Social Sciences, "Kore" University of Enna, 94100 Enna, Italy; Division of Endocrinology (R.M., A.B.), Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; and HUMANITAS (R.V.), Catania Oncology Center, 95126 Catania, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Malaguarnera
authors.affiliation: Department of Clinical and Molecular Bio-Medicine (F.G., V.V., M.L.N., S.L., R.V., F.F.), Endocrinology Unit, Garibaldi-Nesima Medical Center, University of Catania, 95122 Catania, Italy; Immunology and Pharmacotherapy Area (A.F.), Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00165 Rome, Italy; Department of Motor Sciences (V.V.), School of Human and Social Sciences, "Kore" University of Enna, 94100 Enna, Italy; Division of Endocrinology (R.M., A.B.), Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; and HUMANITAS (R.V.), Catania Oncology Center, 95126 Catania, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Belfiore
authors.affiliation: Department of Clinical and Molecular Bio-Medicine (F.G., V.V., M.L.N., S.L., R.V., F.F.), Endocrinology Unit, Garibaldi-Nesima Medical Center, University of Catania, 95122 Catania, Italy; Immunology and Pharmacotherapy Area (A.F.), Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00165 Rome, Italy; Department of Motor Sciences (V.V.), School of Human and Social Sciences, "Kore" University of Enna, 94100 Enna, Italy; Division of Endocrinology (R.M., A.B.), Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; and HUMANITAS (R.V.), Catania Oncology Center, 95126 Catania, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Vigneri
authors.affiliation: Department of Clinical and Molecular Bio-Medicine (F.G., V.V., M.L.N., S.L., R.V., F.F.), Endocrinology Unit, Garibaldi-Nesima Medical Center, University of Catania, 95122 Catania, Italy; Immunology and Pharmacotherapy Area (A.F.), Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00165 Rome, Italy; Department of Motor Sciences (V.V.), School of Human and Social Sciences, "Kore" University of Enna, 94100 Enna, Italy; Division of Endocrinology (R.M., A.B.), Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; and HUMANITAS (R.V.), Catania Oncology Center, 95126 Catania, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Frasca
mesh_terms: D000368:Aged; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*