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Sox2 maintains self-renewal of tumor initiating cells in osteosarcomas

Tumors are thought to be sustained by a reservoir of self-renewing cells, termed tumor initiating cells or cancer stem cells. Osteosarcomas are high-grade sarcomas derived from osteoblast progenitor cells and are the most common pediatric bone malignancy. In this report we show that the stem cell tr...

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Autores principales: Basu-Roy, Upal, Seo, Eunjeong, Ramanathapuram, Lalitha, Rapp, Timothy B., Perry, Jennifer A., Orkin, Stuart H., Mansukhani, Alka, Basilico, Claudio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243769/
https://www.ncbi.nlm.nih.gov/pubmed/21927024
http://dx.doi.org/10.1038/onc.2011.405
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author Basu-Roy, Upal
Seo, Eunjeong
Ramanathapuram, Lalitha
Rapp, Timothy B.
Perry, Jennifer A.
Orkin, Stuart H.
Mansukhani, Alka
Basilico, Claudio
author_facet Basu-Roy, Upal
Seo, Eunjeong
Ramanathapuram, Lalitha
Rapp, Timothy B.
Perry, Jennifer A.
Orkin, Stuart H.
Mansukhani, Alka
Basilico, Claudio
author_sort Basu-Roy, Upal
collection PubMed
description Tumors are thought to be sustained by a reservoir of self-renewing cells, termed tumor initiating cells or cancer stem cells. Osteosarcomas are high-grade sarcomas derived from osteoblast progenitor cells and are the most common pediatric bone malignancy. In this report we show that the stem cell transcription factor Sox2 is highly expressed in human and murine osteosarcoma cell lines as well as in tumor samples. Osteosarcoma cells have increased ability to grow in suspension as osteospheres, that are greatly enriched in expression of Sox2 and the stem cell marker, Sca-1. Depletion of Sox2 by shRNAs in independent murine osteosarcoma-derived cells drastically reduces their transformed properties in vitro and their ability to form tumors. Sox2-depleted osteosarcoma cells can no longer form osteospheres, and differentiate into mature osteoblasts. Concomitantly, they exhibit decreased Sca-1 expression and upregulation of the Wnt signaling pathway. Thus, despite other mutations, these tumor cells maintain a proliferative requirement for Sox2. Our data indicate that Sox2 is required for osteosarcoma cell self-renewal, and that Sox2 antagonizes the pro-differentiation Wnt pathway, that can in turn reduce Sox2 expression. These studies define Sox2 as a survival factor and a novel biomarker of self-renewal in osteosarcomas, and support a tumor suppressive role for the Wnt pathway in tumors of mesenchymal origin. Our findings could provide the basis for novel therapeutic strategies based on inhibiting Sox2 or enhancing Wnt signaling for the treatment of osteosarcomas.
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spelling pubmed-32437692012-11-03 Sox2 maintains self-renewal of tumor initiating cells in osteosarcomas Basu-Roy, Upal Seo, Eunjeong Ramanathapuram, Lalitha Rapp, Timothy B. Perry, Jennifer A. Orkin, Stuart H. Mansukhani, Alka Basilico, Claudio Oncogene Article Tumors are thought to be sustained by a reservoir of self-renewing cells, termed tumor initiating cells or cancer stem cells. Osteosarcomas are high-grade sarcomas derived from osteoblast progenitor cells and are the most common pediatric bone malignancy. In this report we show that the stem cell transcription factor Sox2 is highly expressed in human and murine osteosarcoma cell lines as well as in tumor samples. Osteosarcoma cells have increased ability to grow in suspension as osteospheres, that are greatly enriched in expression of Sox2 and the stem cell marker, Sca-1. Depletion of Sox2 by shRNAs in independent murine osteosarcoma-derived cells drastically reduces their transformed properties in vitro and their ability to form tumors. Sox2-depleted osteosarcoma cells can no longer form osteospheres, and differentiate into mature osteoblasts. Concomitantly, they exhibit decreased Sca-1 expression and upregulation of the Wnt signaling pathway. Thus, despite other mutations, these tumor cells maintain a proliferative requirement for Sox2. Our data indicate that Sox2 is required for osteosarcoma cell self-renewal, and that Sox2 antagonizes the pro-differentiation Wnt pathway, that can in turn reduce Sox2 expression. These studies define Sox2 as a survival factor and a novel biomarker of self-renewal in osteosarcomas, and support a tumor suppressive role for the Wnt pathway in tumors of mesenchymal origin. Our findings could provide the basis for novel therapeutic strategies based on inhibiting Sox2 or enhancing Wnt signaling for the treatment of osteosarcomas. 2011-09-19 2012-05-03 /pmc/articles/PMC3243769/ /pubmed/21927024 http://dx.doi.org/10.1038/onc.2011.405 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Basu-Roy, Upal
Seo, Eunjeong
Ramanathapuram, Lalitha
Rapp, Timothy B.
Perry, Jennifer A.
Orkin, Stuart H.
Mansukhani, Alka
Basilico, Claudio
Sox2 maintains self-renewal of tumor initiating cells in osteosarcomas
title Sox2 maintains self-renewal of tumor initiating cells in osteosarcomas
title_full Sox2 maintains self-renewal of tumor initiating cells in osteosarcomas
title_fullStr Sox2 maintains self-renewal of tumor initiating cells in osteosarcomas
title_full_unstemmed Sox2 maintains self-renewal of tumor initiating cells in osteosarcomas
title_short Sox2 maintains self-renewal of tumor initiating cells in osteosarcomas
title_sort sox2 maintains self-renewal of tumor initiating cells in osteosarcomas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243769/
https://www.ncbi.nlm.nih.gov/pubmed/21927024
http://dx.doi.org/10.1038/onc.2011.405
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