Development and characterization of the novel human osteosarcoma cell line COS-33 with sustained activation of the mTOR pathway

Ashley VanCleave, Mykayla Palmer, Fang Fang, Haydee Torres, Tania Rodezno, Qilin Li, Kirby Fuglsby, Claire Evans, Yohannes Afeworki, Alan Ross, Pulivarthi Rao, Patricia Leiferman, Siyuan Zheng, Peter Houghton, Jianning Tao

Research output: Contribution to journalArticle

Abstract

Outcomes have not improved for metastatic osteosarcoma for several decades. In part, this failure to develop better therapies stems from a lack of understanding of osteosarcoma biology, given the rarity of the disease and the high genetic heterogeneity at the time of diagnosis. We report here the successful establishment of a new human osteosarcoma cell line, COS-33, from a patient-derived xenograft and demonstrate retention of the biological features of the original tumor. We found high mTOR signaling activity in the cultured cells, which were sensitive to a small molecule inhibitor, rapamycin, a suppressor of the mTOR pathway. Suppressed mTOR signaling after treatment with rapamycin was confirmed by decreased phosphorylation of the S6 ribosomal protein. Increasing concentrations of rapamycin progressively inhibited cell proliferation in vitro. We observed significant inhibitory effects of the drug on cell migration, invasion, and colony formation in the cultured cells. Furthermore, we found that only a strong osteogenic inducer, bone morphogenetic protein-2, promoted the cells to differentiate into mature mineralizing osteoblasts, indicating that the COS-33 cell line may have impaired osteoblast differentiation. Grafted COS-33 cells exhibited features typical of osteosarcoma, such as production of osteoid and tumorigenicity in vivo. In addition, we revealed that the COS-33 cell line retained a complex karyotype, a homozygous deletion of the TP53 gene, and typical histological features from its original tumor. Our novel cellular model may provide a valuable platform for studying the etiology and molecular pathogenesis of osteosarcoma as well as for testing novel drugs for future genome-informed targeted therapy.

Original languageEnglish (US)
Pages (from-to)2597-2610
Number of pages14
JournalOncotarget
Volume11
Issue number27
DOIs
StatePublished - Jul 1 2020

Keywords

  • COS-33
  • MTOR
  • Osteogenic differentiation
  • Osteosarcoma
  • TP53

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    VanCleave, A., Palmer, M., Fang, F., Torres, H., Rodezno, T., Li, Q., Fuglsby, K., Evans, C., Afeworki, Y., Ross, A., Rao, P., Leiferman, P., Zheng, S., Houghton, P., & Tao, J. (2020). Development and characterization of the novel human osteosarcoma cell line COS-33 with sustained activation of the mTOR pathway. Oncotarget, 11(27), 2597-2610. https://doi.org/10.18632/oncotarget.27611