Abstract
Giant cell tumor of bone (GCTB), is a rare intermediate malignant bone tumor with high local infiltrative ability, and is genetically characterized by mutation in the H3-3A gene. Standard treatment is curative surgical tumor resection. GCTB demonstrates both local recurrence and pulmonary metastasis after surgical treatment, and effective systematic chemotherapy is yet to be established. Therefore, development of novel chemotherapies for GCTB is necessary. Although patient-derived tumor cell lines are potent tools for preclinical research, 15 GCTB cell lines have been reported to date, and only four are publicly available. Thus, this study aimed to establish and characterize a novel GCTB cell line for preclinical studies on GCTB. Herein, we described the establishment of a cell line, NCC-GCTB5-C1, from the primary tumor tissue of a patient with GCTB. NCC-GCTB5-C1 was shown to harbor a mutation in the H3-3A gene, which is typical of GCTB; thus, it has useful properties for in vitro studies. We conducted the largest integrated screening analysis of 214 antitumor agents using NCC-GCTB5-C1 along with four GCTB cell lines. Romidepsin (a histone deacetylase inhibitor), camptothecin, and actinomycin D (topoisomerase inhibitors) demonstrated remarkable antitumor effects, suggesting that these antitumor agents are potential therapeutic candidates for GCTB treatment. Therefore, the NCC-GCTB5-C1 cell line could potentially contribute to the elucidation of GCTB pathogenesis and the development of novel GCTB treatments.
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18 October 2022
A Correction to this paper has been published: https://doi.org/10.1007/s13577-022-00805-2
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Acknowledgements
We thank Drs. E. Kobayashi, S. Iwata, K.Ogura, S.Osaki, K.Sato, C.Sato, S.Ishihara (Department of Musculoskeletal Oncology), and the National Cancer Center Hospital for sampling tumor tissue specimens from surgically resected materials. We also appreciate the technical assistance provided by Mrs. Y. Kuwata (Division of Rare Cancer Research) and technical support provided by Mrs. Y. Shiotani, Mr. N. Uchiya, and Dr. T. Imai (Central Animal Division, National Cancer Center Research Institute). We would like to thank Editage (www.editage.jp) for providing English language editing services and for their constructive comments on this manuscript. This study was technically assisted by the Fundamental Innovative Oncology Core of the National Cancer Center.
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This research was supported by the Japan Agency for Medical Research and Development (Grant number: 20ck0106537h0002).
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The ethical committee of the National Cancer Center approved the use of clinical materials for this study (approval number: 2004-050). Animal experiments were conducted in compliance with the guidelines of the Institute for Laboratory Animal Research, National Cancer Center Research Institute.
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13577_2022_724_MOESM1_ESM.tiff
Supplementary file1 Short tandem repeat patterns of NCC-GCTB5-C1 and the original tumor tissue (a) Short tandem repeat patterns of the original tumor tissue of NCC-GCTB5-C1 and (b) short tandem repeat patterns of NCC-GCTB5-C1 cells (passage 25) (TIFF 3925 KB)
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Akiyama, T., Yoshimatsu, Y., Noguchi, R. et al. Establishment and characterization of NCC-GCTB5-C1: a novel cell line of giant cell tumor of bone. Human Cell 35, 1621–1629 (2022). https://doi.org/10.1007/s13577-022-00724-2
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DOI: https://doi.org/10.1007/s13577-022-00724-2