SCA-1 Identifies the Tumor-Initiating Cells in Mammary Tumors of BALB-neuT Transgenic Mice
Cancer stem cells, initiating and sustaining the tumor process, have been isolated in human and murine breast cancer using different cell markers. In the present study, we aimed to evaluate the presence and characteristics of stem/tumor-initiating cells in the model of the mouse mammary neoplasia dr...
Main Authors: | , , , , |
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Format: | Article |
Language: | English |
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Elsevier
2008-12-01
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Series: | Neoplasia: An International Journal for Oncology Research |
Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558608800887 |
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author | Cristina Grange Stefania Lanzardo Federica Cavallo Giovanni Camussi Benedetta Bussolati |
author_facet | Cristina Grange Stefania Lanzardo Federica Cavallo Giovanni Camussi Benedetta Bussolati |
author_sort | Cristina Grange |
collection | DOAJ |
description | Cancer stem cells, initiating and sustaining the tumor process, have been isolated in human and murine breast cancer using different cell markers. In the present study, we aimed to evaluate the presence and characteristics of stem/tumor-initiating cells in the model of the mouse mammary neoplasia driven by the activated form of rat Her-2/neu oncogene (BALB-neuT mice). For this purpose, we generated tumor spheres from primary spontaneous BALB-neuT tumors. Tumor sphere cultures were characterized for clonogenicity, self-renewal, and ability to differentiate in epithelial/myoepithelial cells of the mammary gland expressing basal and luminal cytokeratins and alpha-smooth muscle actin. In addition, tumor spheres were more resistant to doxorubicin compared with parental tumor cells. In the attempt to identify a selected marker for the sphere-generating cells, we found that Sca-1+ cells, present in tumors or enriched in mammospheres, and not CD24+ or CD29+ cells, were responsible for the sphere generation in vitro. Moreover, cells from the tumor spheres showed an increased tumor-generating ability in respect to the epithelial tumor cells. Sca-1+ sorted cells or clonal mammospheres derived from a Sca-1+ cell showed a superimposable tumor-initiating ability. The data of the present study indicate that a Sca-1+ population derived from mammary BALB-neuT tumors is responsible for sphere generation in culture and for initiating tumors in vivo. |
first_indexed | 2024-12-18T04:40:37Z |
format | Article |
id | doaj.art-649323e8d7094e649ce5bff7e2572f94 |
institution | Directory Open Access Journal |
issn | 1476-5586 1522-8002 |
language | English |
last_indexed | 2024-12-18T04:40:37Z |
publishDate | 2008-12-01 |
publisher | Elsevier |
record_format | Article |
series | Neoplasia: An International Journal for Oncology Research |
spelling | doaj.art-649323e8d7094e649ce5bff7e2572f942022-12-21T21:20:43ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022008-12-0110121433144310.1593/neo.08902SCA-1 Identifies the Tumor-Initiating Cells in Mammary Tumors of BALB-neuT Transgenic MiceCristina Grange0Stefania Lanzardo1Federica Cavallo2Giovanni Camussi3Benedetta Bussolati4Department of Internal Medicine, Molecular Biotechnology Center, University of Torino, Torino, ItalyDepartment of Biological Sciences, Molecular Biotechnology Center, University of Torino, Torino, ItalyDepartment of Biological Sciences, Molecular Biotechnology Center, University of Torino, Torino, ItalyDepartment of Internal Medicine, Molecular Biotechnology Center, University of Torino, Torino, ItalyDepartment of Internal Medicine, Molecular Biotechnology Center, University of Torino, Torino, ItalyCancer stem cells, initiating and sustaining the tumor process, have been isolated in human and murine breast cancer using different cell markers. In the present study, we aimed to evaluate the presence and characteristics of stem/tumor-initiating cells in the model of the mouse mammary neoplasia driven by the activated form of rat Her-2/neu oncogene (BALB-neuT mice). For this purpose, we generated tumor spheres from primary spontaneous BALB-neuT tumors. Tumor sphere cultures were characterized for clonogenicity, self-renewal, and ability to differentiate in epithelial/myoepithelial cells of the mammary gland expressing basal and luminal cytokeratins and alpha-smooth muscle actin. In addition, tumor spheres were more resistant to doxorubicin compared with parental tumor cells. In the attempt to identify a selected marker for the sphere-generating cells, we found that Sca-1+ cells, present in tumors or enriched in mammospheres, and not CD24+ or CD29+ cells, were responsible for the sphere generation in vitro. Moreover, cells from the tumor spheres showed an increased tumor-generating ability in respect to the epithelial tumor cells. Sca-1+ sorted cells or clonal mammospheres derived from a Sca-1+ cell showed a superimposable tumor-initiating ability. The data of the present study indicate that a Sca-1+ population derived from mammary BALB-neuT tumors is responsible for sphere generation in culture and for initiating tumors in vivo.http://www.sciencedirect.com/science/article/pii/S1476558608800887 |
spellingShingle | Cristina Grange Stefania Lanzardo Federica Cavallo Giovanni Camussi Benedetta Bussolati SCA-1 Identifies the Tumor-Initiating Cells in Mammary Tumors of BALB-neuT Transgenic Mice Neoplasia: An International Journal for Oncology Research |
title | SCA-1 Identifies the Tumor-Initiating Cells in Mammary Tumors of BALB-neuT Transgenic Mice |
title_full | SCA-1 Identifies the Tumor-Initiating Cells in Mammary Tumors of BALB-neuT Transgenic Mice |
title_fullStr | SCA-1 Identifies the Tumor-Initiating Cells in Mammary Tumors of BALB-neuT Transgenic Mice |
title_full_unstemmed | SCA-1 Identifies the Tumor-Initiating Cells in Mammary Tumors of BALB-neuT Transgenic Mice |
title_short | SCA-1 Identifies the Tumor-Initiating Cells in Mammary Tumors of BALB-neuT Transgenic Mice |
title_sort | sca 1 identifies the tumor initiating cells in mammary tumors of balb neut transgenic mice |
url | http://www.sciencedirect.com/science/article/pii/S1476558608800887 |
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