title: Salinomycin inhibits osteosarcoma by targeting its tumor stem cells.
abstract: 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.
authors.affiliation: Department of Musculoskeletal Oncology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Qing-Lian
authors.initials: QL
authors.lastname: Tang
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Zhao
authors.forename: Jin-Chun
authors.initials: JC
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Liang
authors.forename: Jun-Qiang
authors.initials: JQ
authors.lastname: Yin
authors.forename: Chang-Ye
authors.initials: CY
authors.lastname: Zou
authors.forename: Xian-Biao
authors.initials: XB
authors.lastname: Xie
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Jing-Nan
authors.initials: JN
authors.lastname: Shen
authors.forename: Tiebang
authors.initials: T
authors.lastname: Kang
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
mesh_terms: D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D011714:Pyrans / Q000494:pharmacology*; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis; D060449:Wnt Signaling Pathway / Q000187:drug effects; D000095662:Polyether Polyketides
chemical_list: D050814:Octamer Transcription Factor-3; D011714:Pyrans; D055748:SOXB1 Transcription Factors; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; C010327:salinomycin; D000095662:Polyether Polyketides