Transforming growth factor β1 signal is crucial for dedifferentiation of cancer cells to cancer stem cells in osteosarcoma

Zhang, Haixia, Wu, Haotong, Zheng, Junheng, Yu, Pei, Xu, Lixiao, Jiang, Pan, Gao, Jin, Wang, Hua, and Zhang, Yan (2013) Transforming growth factor β1 signal is crucial for dedifferentiation of cancer cells to cancer stem cells in osteosarcoma. Stem Cells, 31 (3). pp. 433-446.

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Abstract

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.

Item ID: 25300
Item Type: Article (Research - C1)
ISSN: 1549-4918
Keywords: TGF-β1; osteosarcoma; cancer stem cell; dedifferentiation; vascular endothelial cells; hypoxia
Date Deposited: 06 Mar 2013 05:53
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111201 Cancer Cell Biology @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 100%
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