Thyrospheres from normal or malignant thyroid tissue have different biological, functional, and genetic features

Fiorenza Gianì, Veronica Vella, Maria Luisa Nicolosi, Alessandra Fierabracci, Sonia Lotta, Roberta Malaguarnera, Antonino Belfiore, Riccardo Vigneri, Francesco Frasca

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Context: 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. Objectives: The objective of the studywasto 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. Design: Thyrospheres from PTCs and NTs were isolated. Main Outcome Measures: 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.

Original languageEnglish
Pages (from-to)E1168-E1178
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number9
DOIs
Publication statusPublished - Sep 1 2015

Fingerprint

Thyroid Gland
Tissue
Thyroid Neoplasms
Stem Cells
Stem cells
Factor IX
Neoplastic Stem Cells
Gene Expression
Fluorescent Antibody Technique
Gene expression
Papillary Thyroid cancer
Microarray Analysis
Heterografts
Real-Time Polymerase Chain Reaction
Neoplasms
Fluorescence
Outcome Assessment (Health Care)
Cell Line
Microarrays
Tumors

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Thyrospheres from normal or malignant thyroid tissue have different biological, functional, and genetic features. / Gianì, Fiorenza; Vella, Veronica; Nicolosi, Maria Luisa; Fierabracci, Alessandra; Lotta, Sonia; Malaguarnera, Roberta; Belfiore, Antonino; Vigneri, Riccardo; Frasca, Francesco.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 100, No. 9, 01.09.2015, p. E1168-E1178.

Research output: Contribution to journalArticle

Gianì, F, Vella, V, Nicolosi, ML, Fierabracci, A, Lotta, S, Malaguarnera, R, Belfiore, A, Vigneri, R & Frasca, F 2015, 'Thyrospheres from normal or malignant thyroid tissue have different biological, functional, and genetic features', Journal of Clinical Endocrinology and Metabolism, vol. 100, no. 9, pp. E1168-E1178. https://doi.org/10.1210/jc.2014-4163
Gianì, Fiorenza ; Vella, Veronica ; Nicolosi, Maria Luisa ; Fierabracci, Alessandra ; Lotta, Sonia ; Malaguarnera, Roberta ; Belfiore, Antonino ; Vigneri, Riccardo ; Frasca, Francesco. / Thyrospheres from normal or malignant thyroid tissue have different biological, functional, and genetic features. In: Journal of Clinical Endocrinology and Metabolism. 2015 ; Vol. 100, No. 9. pp. E1168-E1178.
@article{8c59f1c5dce448fbbd8656cb62d80331,
title = "Thyrospheres from normal or malignant thyroid tissue have different biological, functional, and genetic features",
abstract = "Context: 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. Objectives: The objective of the studywasto 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. Design: Thyrospheres from PTCs and NTs were isolated. Main Outcome Measures: 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.",
author = "Fiorenza Gian{\`i} and Veronica Vella and Nicolosi, {Maria Luisa} and Alessandra Fierabracci and Sonia Lotta and Roberta Malaguarnera and Antonino Belfiore and Riccardo Vigneri and Francesco Frasca",
year = "2015",
month = "9",
day = "1",
doi = "10.1210/jc.2014-4163",
language = "English",
volume = "100",
pages = "E1168--E1178",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "9",

}

TY - JOUR

T1 - Thyrospheres from normal or malignant thyroid tissue have different biological, functional, and genetic features

AU - Gianì, Fiorenza

AU - Vella, Veronica

AU - Nicolosi, Maria Luisa

AU - Fierabracci, Alessandra

AU - Lotta, Sonia

AU - Malaguarnera, Roberta

AU - Belfiore, Antonino

AU - Vigneri, Riccardo

AU - Frasca, Francesco

PY - 2015/9/1

Y1 - 2015/9/1

N2 - Context: 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. Objectives: The objective of the studywasto 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. Design: Thyrospheres from PTCs and NTs were isolated. Main Outcome Measures: 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.

AB - Context: 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. Objectives: The objective of the studywasto 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. Design: Thyrospheres from PTCs and NTs were isolated. Main Outcome Measures: 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.

UR - http://www.scopus.com/inward/record.url?scp=84941687237&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941687237&partnerID=8YFLogxK

U2 - 10.1210/jc.2014-4163

DO - 10.1210/jc.2014-4163

M3 - Article

C2 - 26151334

AN - SCOPUS:84941687237

VL - 100

SP - E1168-E1178

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 9

ER -