Salinomycin inhibits osteosarcoma by targeting its tumor stem cells

Highlights ► We have utilized three different methods to enrich TSCs in osteosarcoma. ► Salinomycin could selectively target TSCs in osteosarcoma both in vitro and in vivo . ► Wnt/β-catenin signaling pathway may be involved in this inhibition of salinomycin. ► Salinomycin is an effective inhibitor o...

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Published in	Cancer letters Vol. 311; no. 1; pp. 113 - 121
Main Authors	Tang, Qing-Lian, Zhao, Zhi-Qiang, Li, Jin-chun, Liang, Yi, Yin, Jun-Qiang, Zou, Chang-Ye, Xie, Xian-Biao, Zeng, Yi-Xin, Shen, Jing-Nan, Kang, Tiebang, Wang, Jin
Format	Journal Article
Language	English
Published	Ireland Elsevier Ireland Ltd 01.12.2011 Elsevier Limited
Subjects	Adolescence Bone marrow Bone Neoplasms - drug therapy Bone Neoplasms - metabolism Bone Neoplasms - pathology Bone tumors Cell Line, Tumor Chemotherapy Children Cloning Down-Regulation - drug effects Drug Resistance, Neoplasm Experiments Hematology, Oncology and Palliative Medicine Humans Immunohistochemistry Metastases Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - metabolism Neoplastic Stem Cells - pathology Oct-4 protein Octamer Transcription Factor-3 - biosynthesis Osteosarcoma Osteosarcoma - drug therapy Osteosarcoma - metabolism Osteosarcoma - pathology Osteosarcoma cells Overexpression Prognosis Proteins Pyrans - pharmacology Salinomycin Side effects Signal transduction SOXB1 Transcription Factors - biosynthesis Stem cells Surgery Tumor stem cell Wnt protein Wnt Signaling Pathway - drug effects Wnt/β-catenin Chemotherapy Salinomycin Osteosarcoma Wnt/β-catenin Tumor stem cell
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Abstract	Highlights ► We have utilized three different methods to enrich TSCs in osteosarcoma. ► Salinomycin could selectively target TSCs in osteosarcoma both in vitro and in vivo . ► Wnt/β-catenin signaling pathway may be involved in this inhibition of salinomycin. ► Salinomycin is an effective inhibitor of osteosarcoma stem cells.
AbstractList	Osteosarcoma is the most common primary bone tumor in children and adolescents and is typically associated with a poor prognosis. Tumor stem cells (TSCs) are presumed to drive tumor initiation and tumor relapse or metastasis. Hence, the poor prognosis of osteosarcoma likely results from a failure to target the osteosarcoma stem cells. Here, we have utilized three different methods to enrich TSCs in osteosarcoma and further evaluated whether salinomycin could selectively target TSCs in osteosarcoma. Our results indicated that sarcosphere selection, chemotherapy selection and stem cell marker OCT4 or SOX2 over-expression are all effective in the enrichment of TSCs from osteosarcoma cell lines. Further investigation found that salinomycin inhibited osteosarcoma by selectively targeting its stem cells both in vitro and in vivo without severe side effects, and the Wnt/β-catenin signaling pathway may be involved in this inhibition of salinomycin. Taken together, we have identified that salinomycin is an effective inhibitor of osteosarcoma stem cells, supporting the use of salinomycin for elimination of osteosarcoma stem cells and implying a need for further clinical evaluation. Highlights * We have utilized three different methods to enrich TSCs in osteosarcoma. * Salinomycin could selectively target TSCs in osteosarcoma bothin vitroandin vivo. * Wnt/β-catenin signaling pathway may be involved in this inhibition of salinomycin. * Salinomycin is an effective inhibitor of osteosarcoma stem cells. ► We have utilized three different methods to enrich TSCs in osteosarcoma. ► Salinomycin could selectively target TSCs in osteosarcoma both in vitro and in vivo. ► Wnt/β-catenin signaling pathway may be involved in this inhibition of salinomycin. ► Salinomycin is an effective inhibitor of osteosarcoma stem cells. Osteosarcoma is the most common primary bone tumor in children and adolescents and is typically associated with a poor prognosis. Tumor stem cells (TSCs) are presumed to drive tumor initiation and tumor relapse or metastasis. Hence, the poor prognosis of osteosarcoma likely results from a failure to target the osteosarcoma stem cells. Here, we have utilized three different methods to enrich TSCs in osteosarcoma and further evaluated whether salinomycin could selectively target TSCs in osteosarcoma. Our results indicated that sarcosphere selection, chemotherapy selection and stem cell marker OCT4 or SOX2 over-expression are all effective in the enrichment of TSCs from osteosarcoma cell lines. Further investigation found that salinomycin inhibited osteosarcoma by selectively targeting its stem cells both in vitro and in vivo without severe side effects, and the Wnt/β-catenin signaling pathway may be involved in this inhibition of salinomycin. Taken together, we have identified that salinomycin is an effective inhibitor of osteosarcoma stem cells, supporting the use of salinomycin for elimination of osteosarcoma stem cells and implying a need for further clinical evaluation. Osteosarcoma is the most common primary bone tumor in children and adolescents and is typically associated with a poor prognosis. Tumor stem cells (TSCs) are presumed to drive tumor initiation and tumor relapse or metastasis. Hence, the poor prognosis of osteosarcoma likely results from a failure to target the osteosarcoma stem cells. Here, we have utilized three different methods to enrich TSCs in osteosarcoma and further evaluated whether salinomycin could selectively target TSCs in osteosarcoma. Our results indicated that sarcosphere selection, chemotherapy selection and stem cell marker OCT4 or SOX2 over-expression are all effective in the enrichment of TSCs from osteosarcoma cell lines. Further investigation found that salinomycin inhibited osteosarcoma by selectively targeting its stem cells both in vitro and in vivo without severe side effects, and the Wnt/[beta]-catenin signaling pathway may be involved in this inhibition of salinomycin. Taken together, we have identified that salinomycin is an effective inhibitor of osteosarcoma stem cells, supporting the use of salinomycin for elimination of osteosarcoma stem cells and implying a need for further clinical evaluation. Highlights ► We have utilized three different methods to enrich TSCs in osteosarcoma. ► Salinomycin could selectively target TSCs in osteosarcoma both in vitro and in vivo . ► Wnt/β-catenin signaling pathway may be involved in this inhibition of salinomycin. ► Salinomycin is an effective inhibitor of osteosarcoma stem cells.
Author	Tang, Qing-Lian Zeng, Yi-Xin Xie, Xian-Biao Li, Jin-chun Kang, Tiebang Wang, Jin Liang, Yi Yin, Jun-Qiang Zou, Chang-Ye Zhao, Zhi-Qiang Shen, Jing-Nan
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Keywords	Chemotherapy Salinomycin Osteosarcoma Wnt/β-catenin Tumor stem cell
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Snippet	Highlights ► We have utilized three different methods to enrich TSCs in osteosarcoma. ► Salinomycin could selectively target TSCs in osteosarcoma both in vitro... ► We have utilized three different methods to enrich TSCs in osteosarcoma. ► Salinomycin could selectively target TSCs in osteosarcoma both in vitro and in... Osteosarcoma is the most common primary bone tumor in children and adolescents and is typically associated with a poor prognosis. Tumor stem cells (TSCs) are... Highlights * We have utilized three different methods to enrich TSCs in osteosarcoma. * Salinomycin could selectively target TSCs in osteosarcoma bothin...
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SubjectTerms	Adolescence Bone marrow Bone Neoplasms - drug therapy Bone Neoplasms - metabolism Bone Neoplasms - pathology Bone tumors Cell Line, Tumor Chemotherapy Children Cloning Down-Regulation - drug effects Drug Resistance, Neoplasm Experiments Hematology, Oncology and Palliative Medicine Humans Immunohistochemistry Metastases Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - metabolism Neoplastic Stem Cells - pathology Oct-4 protein Octamer Transcription Factor-3 - biosynthesis Osteosarcoma Osteosarcoma - drug therapy Osteosarcoma - metabolism Osteosarcoma - pathology Osteosarcoma cells Overexpression Prognosis Proteins Pyrans - pharmacology Salinomycin Side effects Signal transduction SOXB1 Transcription Factors - biosynthesis Stem cells Surgery Tumor stem cell Wnt protein Wnt Signaling Pathway - drug effects Wnt/β-catenin
Title	Salinomycin inhibits osteosarcoma by targeting its tumor stem cells
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