Osteosarcoma (OS) is a highly malignant bone
tumor and the prognosis for non-responders to
chemotherapy remains poor. Previous studies have shown that human
sarcomas contain
sarcoma-initiating 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-related 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 (OSHIGH ) and counterpart clones. OSHIGH cells showed chemoresistance and their metabolism highly depended on aerobic glycolysis and suppressed oxidative phosphorylation. Using
RNA-sequencing, we identified LIN28B as a SIC-related gene highly expressed in OSHIGH cells.
mRNA of LIN28B 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 LIN28B in OS13 cells reduced
tumorigenesis, decreased chemoresistance, and reversed oxidative phosphorylation function. Combination
therapy consisting of a glycolysis inhibitor and low-dose
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-called
cancer/testis antigen, might be a good approach.