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In Vitro Identification and Characterization of CD133(pos) Cancer Stem-Like Cells in Anaplastic Thyroid Carcinoma Cell Lines
BACKGROUND: Recent publications suggest that neoplastic initiation and growth are dependent on a small subset of cells, termed cancer stem cells (CSCs). Anaplastic Thyroid Carcinoma (ATC) is a very aggressive solid tumor with poor prognosis, characterized by high dedifferentiation. The existence of...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2568821/ https://www.ncbi.nlm.nih.gov/pubmed/18958156 http://dx.doi.org/10.1371/journal.pone.0003544 |
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author | Zito, Giovanni Richiusa, Pierina Bommarito, Alessandra Carissimi, Elvira Russo, Leonardo Coppola, Antonina Zerilli, Monica Rodolico, Vito Criscimanna, Angela Amato, Marco Pizzolanti, Giuseppe Galluzzo, Aldo Giordano, Carla |
author_facet | Zito, Giovanni Richiusa, Pierina Bommarito, Alessandra Carissimi, Elvira Russo, Leonardo Coppola, Antonina Zerilli, Monica Rodolico, Vito Criscimanna, Angela Amato, Marco Pizzolanti, Giuseppe Galluzzo, Aldo Giordano, Carla |
author_sort | Zito, Giovanni |
collection | PubMed |
description | BACKGROUND: Recent publications suggest that neoplastic initiation and growth are dependent on a small subset of cells, termed cancer stem cells (CSCs). Anaplastic Thyroid Carcinoma (ATC) is a very aggressive solid tumor with poor prognosis, characterized by high dedifferentiation. The existence of CSCs might account for the heterogeneity of ATC lesions. CD133 has been identified as a stem cell marker for normal and cancerous tissues, although its biological function remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: ATC cell lines ARO, KAT-4, KAT-18 and FRO were analyzed for CD133 expression. Flow cytometry showed CD133(pos) cells only in ARO and KAT-4 (64±9% and 57±12%, respectively). These data were confirmed by qRT-PCR and immunocytochemistry. ARO and KAT-4 were also positive for fetal marker oncofetal fibronectin and negative for thyrocyte-specific differentiating markers thyroglobulin, thyroperoxidase and sodium/iodide symporter. Sorted ARO/CD133(pos) cells exhibited higher proliferation, self-renewal, colony-forming ability in comparison with ARO/CD133(neg). Furthermore, ARO/CD133(pos) showed levels of thyroid transcription factor TTF-1 similar to the fetal thyroid cell line TAD-2, while the expression in ARO/CD133(neg) was negligible. The expression of the stem cell marker OCT-4 detected by RT-PCR and flow cytometry was markedly higher in ARO/CD133(pos) in comparison to ARO/CD133(neg) cells. The stem cell markers c-KIT and THY-1 were negative. Sensitivity to chemotherapy agents was investigated, showing remarkable resistance to chemotherapy-induced apoptosis in ARO/CD133(pos) when compared with ARO/CD133(neg) cells. CONCLUSIONS/SIGNIFICANCE: We describe CD133(pos) cells in ATC cell lines. ARO/CD133(pos) cells exhibit stem cell-like features - such as high proliferation, self-renewal ability, expression of OCT-4 - and are characterized by higher resistance to chemotherapy. The simultaneous positivity for thyroid specific factor TTF-1 and onfFN suggest they might represent putative thyroid cancer stem-like cells. Our in vitro findings might provide new insights for novel therapeutic approaches. |
format | Text |
id | pubmed-2568821 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-25688212008-10-28 In Vitro Identification and Characterization of CD133(pos) Cancer Stem-Like Cells in Anaplastic Thyroid Carcinoma Cell Lines Zito, Giovanni Richiusa, Pierina Bommarito, Alessandra Carissimi, Elvira Russo, Leonardo Coppola, Antonina Zerilli, Monica Rodolico, Vito Criscimanna, Angela Amato, Marco Pizzolanti, Giuseppe Galluzzo, Aldo Giordano, Carla PLoS One Research Article BACKGROUND: Recent publications suggest that neoplastic initiation and growth are dependent on a small subset of cells, termed cancer stem cells (CSCs). Anaplastic Thyroid Carcinoma (ATC) is a very aggressive solid tumor with poor prognosis, characterized by high dedifferentiation. The existence of CSCs might account for the heterogeneity of ATC lesions. CD133 has been identified as a stem cell marker for normal and cancerous tissues, although its biological function remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: ATC cell lines ARO, KAT-4, KAT-18 and FRO were analyzed for CD133 expression. Flow cytometry showed CD133(pos) cells only in ARO and KAT-4 (64±9% and 57±12%, respectively). These data were confirmed by qRT-PCR and immunocytochemistry. ARO and KAT-4 were also positive for fetal marker oncofetal fibronectin and negative for thyrocyte-specific differentiating markers thyroglobulin, thyroperoxidase and sodium/iodide symporter. Sorted ARO/CD133(pos) cells exhibited higher proliferation, self-renewal, colony-forming ability in comparison with ARO/CD133(neg). Furthermore, ARO/CD133(pos) showed levels of thyroid transcription factor TTF-1 similar to the fetal thyroid cell line TAD-2, while the expression in ARO/CD133(neg) was negligible. The expression of the stem cell marker OCT-4 detected by RT-PCR and flow cytometry was markedly higher in ARO/CD133(pos) in comparison to ARO/CD133(neg) cells. The stem cell markers c-KIT and THY-1 were negative. Sensitivity to chemotherapy agents was investigated, showing remarkable resistance to chemotherapy-induced apoptosis in ARO/CD133(pos) when compared with ARO/CD133(neg) cells. CONCLUSIONS/SIGNIFICANCE: We describe CD133(pos) cells in ATC cell lines. ARO/CD133(pos) cells exhibit stem cell-like features - such as high proliferation, self-renewal ability, expression of OCT-4 - and are characterized by higher resistance to chemotherapy. The simultaneous positivity for thyroid specific factor TTF-1 and onfFN suggest they might represent putative thyroid cancer stem-like cells. Our in vitro findings might provide new insights for novel therapeutic approaches. Public Library of Science 2008-10-28 /pmc/articles/PMC2568821/ /pubmed/18958156 http://dx.doi.org/10.1371/journal.pone.0003544 Text en Zito et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Zito, Giovanni Richiusa, Pierina Bommarito, Alessandra Carissimi, Elvira Russo, Leonardo Coppola, Antonina Zerilli, Monica Rodolico, Vito Criscimanna, Angela Amato, Marco Pizzolanti, Giuseppe Galluzzo, Aldo Giordano, Carla In Vitro Identification and Characterization of CD133(pos) Cancer Stem-Like Cells in Anaplastic Thyroid Carcinoma Cell Lines |
title |
In Vitro Identification and Characterization of CD133(pos) Cancer Stem-Like Cells in Anaplastic Thyroid Carcinoma Cell Lines |
title_full |
In Vitro Identification and Characterization of CD133(pos) Cancer Stem-Like Cells in Anaplastic Thyroid Carcinoma Cell Lines |
title_fullStr |
In Vitro Identification and Characterization of CD133(pos) Cancer Stem-Like Cells in Anaplastic Thyroid Carcinoma Cell Lines |
title_full_unstemmed |
In Vitro Identification and Characterization of CD133(pos) Cancer Stem-Like Cells in Anaplastic Thyroid Carcinoma Cell Lines |
title_short |
In Vitro Identification and Characterization of CD133(pos) Cancer Stem-Like Cells in Anaplastic Thyroid Carcinoma Cell Lines |
title_sort | in vitro identification and characterization of cd133(pos) cancer stem-like cells in anaplastic thyroid carcinoma cell lines |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2568821/ https://www.ncbi.nlm.nih.gov/pubmed/18958156 http://dx.doi.org/10.1371/journal.pone.0003544 |
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