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...

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Main Authors: Cristina Grange, Stefania Lanzardo, Federica Cavallo, Giovanni Camussi, Benedetta Bussolati
Format: Article
Language:English
Published: Elsevier 2008-12-01
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.
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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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