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Previous studies have shown that human sarcomas contain sarcoma\u2010initiating cells (SIC), which have the characteristics of high tumorigenesis and resistance to chemotherapy. In the present study, we characterized SIC of a novel OS cell line, screened for SIC\u2010related genes, and tried to regulate the proliferation of OS by metabolic interference. Initially, we established a new human OS cell line (OS13) and isolated clones showing higher tumorigenesis as SIC (OS<jats:sup>HIGH<\/jats:sup>) and counterpart clones. OS<jats:sup>HIGH<\/jats:sup> cells showed chemoresistance and their metabolism highly depended on aerobic glycolysis and suppressed oxidative phosphorylation. Using RNA\u2010sequencing, we identified LIN28B as a SIC\u2010related gene highly expressed in OS<jats:sup>HIGH<\/jats:sup> cells. mRNA of <jats:italic>LIN28B<\/jats:italic> was expressed in sarcoma cell lines including OS13, but its expression was not detectable in normal organs other than the testis and placenta. LIN28B protein was also detected in various sarcoma tissues. Knockdown of <jats:italic>LIN28B<\/jats:italic> in OS13 cells reduced tumorigenesis, decreased chemoresistance, and reversed oxidative phosphorylation function. Combination therapy consisting of a glycolysis inhibitor and low\u2010dose chemotherapy had antitumor effects. In conclusion, manipulation of glycolysis combined with chemotherapy might be a good adjuvant treatment for OS. Development of immunotherapy targeting LIN28B, a so\u2010called cancer\/testis antigen, might be a good approach.<\/jats:p>","DOI":"10.1111\/cas.14229","type":"journal-article","created":{"date-parts":[[2019,11,9]],"date-time":"2019-11-09T09:37:50Z","timestamp":1573292270000},"page":"36-46","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Osteosarcoma\u2010initiating cells show high aerobic glycolysis and attenuation of oxidative phosphorylation mediated by LIN28B"],"prefix":"10.1111","volume":"111","author":[{"given":"Emi","family":"Mizushima","sequence":"first","affiliation":[{"name":"Department of Pathology Sapporo Medical University School of Medicine Sapporo Japan"},{"name":"Department of Orthopaedic Surgery Sapporo Medical University School of Medicine Sapporo 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