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Cancer Stem Cells
Version of Record online: 25 FEB 2013
Copyright © 2012 AlphaMed Press
Volume 31, Issue 3, pages 433–446, March 2013
How to Cite
Zhang, H., Wu, H., Zheng, J., Yu, P., Xu, L., Jiang, P., Gao, J., Wang, H. and Zhang, Y. (2013), Transforming Growth Factor β1 Signal is Crucial for Dedifferentiation of Cancer Cells to Cancer Stem Cells in Osteosarcoma. STEM CELLS, 31: 433–446. doi: 10.1002/stem.1298
Author contributions: H.Z.: conception and design, data analysis and interpretation, manuscript writing, and final approval of manuscript; H.W.: collection and assembly of data and data analysis; J.Z.: collection and/or assembly of data, interpretation; P.Y., L.X., and P.J.: collection and/or assembly of data; J.G.: provision of study materials and final approval of manuscript; H.W.: collection and/or assembly of data and final approval of manuscript; Y.Z.: conception and design, financial support, provision of study materials, manuscript writing, and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS November 15, 2012.
- Issue online: 25 FEB 2013
- Version of Record online: 25 FEB 2013
- Accepted manuscript online: 7 DEC 2012 05:39AM EST
- Manuscript Accepted: 15 NOV 2012
- Manuscript Revised: 1 NOV 2012
- Manuscript Received: 2 JUN 2012
- State High-Tech Development Project. Grant Number: 2008AA092604
- National Basic Research Program. Grant Number: 2009CB945400
- Guangdong Planning Project of Science and Technology. Grant Number: 2009B030803037
- Cancer stem cell;
- Vascular endothelial cells;
Human osteosarcoma harbors a small subpopulation of cancer stem cells (CSCs) that is believed to be associated with tumor metastasis, radioresistance/chemoresistance, local invasion, and poor clinical outcome. In this study, we found that transforming growth factor β1 (TGF-β1) signaling and a hypoxic environment dramatically induced self-renewal capacity in non-stem osteosarcoma cells, which in turn promoted chemoresistance, tumorigenicity, neovasculogenesis, and metastatic potential. Furthermore, blocking the TGF-β1 signaling pathway resulted in the inhibition of the dedifferentiation and clonogenicity of osteosarcoma cells, and the reduction of CSC self-renewal capacity and hypoxia-mediated dedifferentiation. These findings demonstrate that stem cells and non-stem cells exist in a dynamic equilibrium within the osteosarcoma cell population, and that CSCs may develop de novo from differentiated cancer cells. Hierarchical models of mammalian CSCs, therefore, should be considered to serve as bidirectional interconversion between the stem and non-stem cell components of the tumor. STEM CELLS2013;31:433–446