Skip to main content
SpringerLink
Log in

Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone: NCC-GCTB8-C1 and NCC-GCTB9-C1

  • Cell Line
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

Giant cell tumor of bone (GCTB) is a rare osteolytic bone tumor consisting of mononuclear stromal cells, macrophages, and osteoclast-like giant cells. Although GCTB predominantly exhibits benign behavior, the tumor carries a significant risk of high local recurrence. Furthermore, GCTB can occasionally undergo malignant transformation and distal metastasis, making it potentially fatal. The standard treatment is complete surgical resection; nonetheless, an optimal treatment strategy for advanced GCTB remains unestablished, necessitating expanded preclinical research to identify appropriate therapeutic options. However, only one GCTB cell line is publicly available from a cell bank for research use worldwide. The present study reports the establishment of two novel cell lines, NCC-GCTB8-C1 and NCC-GCTB9-C1, derived from the primary tumor tissues of two patients with GCTB. Both cell lines maintained the hallmark mutation in the H3-3A gene, which is associated with tumor formation and development in GCTB. Characterization of these cell lines revealed their steady growth, spheroid-formation capability, and invasive traits. Potential therapeutic agents were identified via extensive drug screening of the two cell lines and seven previously established GCTB cell lines. Among the 214 antitumor agents tested, romidepsin, a histone deacetylase inhibitor, and mitoxantrone, a topoisomerase inhibitor, were identified as potential therapeutic agents against GCTB. Conclusively, the establishment of NCC-GCTB8-C1 and NCC-GCTB9-C1 provides novel and crucial resources that are expected to advance GCTB research and potentially revolutionize treatment strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

Data will be available under reasonable conditions.

References

  1. board WHOcte. Soft tissue and bone tumours. 5th ed. World Health Organization classification of tumours. World Health Organization. International Agency for Research on Cancer; 2020.

  2. Nagano A, Urakawa H, Tanaka K, Ozaki T. Current management of giant-cell tumor of bone in the denosumab era. Jpn J Clin Oncol. 2022;52(5):411–6. https://doi.org/10.1093/jjco/hyac018.

    Article  PubMed  Google Scholar 

  3. Turcotte RE. Giant cell tumor of bone. Orthop Clin North Am. 2006;37(1):35–51. https://doi.org/10.1016/j.ocl.2005.08.005.

    Article  PubMed  Google Scholar 

  4. Rekhi B, Dave V. Giant cell tumor of bone: an update, including spectrum of pathological features, pathogenesis, molecular profile and the differential diagnoses. Histol Histopathol. 2023;38(2):139–53. https://doi.org/10.14670/hh-18-486.

    Article  CAS  PubMed  Google Scholar 

  5. Basu Mallick A, Chawla SP. Giant cell tumor of bone: an update. Curr Oncol Rep. 2021;23(5):51. https://doi.org/10.1007/s11912-021-01047-5.

    Article  CAS  PubMed  Google Scholar 

  6. Noguchi R, Yoshimatsu Y, Ono T, Sei A, Hirabayashi K, Ozawa I, et al. Establishment and characterization of NCC-GCTB1-C1: a novel patient-derived cancer cell line of giant cell tumor of bone. Hum Cell. 2020;33(4):1321–8. https://doi.org/10.1007/s13577-020-00415-w.

    Article  CAS  PubMed  Google Scholar 

  7. Yamamoto H, Ishihara S, Toda Y, Oda Y. Histone H3.3 mutation in giant cell tumor of bone: an update in pathology. Med Mol Morphol. 2020;53(1):1–6. https://doi.org/10.1007/s00795-019-00238-1.

    Article  CAS  PubMed  Google Scholar 

  8. Taylor EL, Westendorf JJ. Histone mutations and bone cancers. Adv Exp Med Biol. 2021;1283:53–62. https://doi.org/10.1007/978-981-15-8104-5_4.

    Article  CAS  PubMed  Google Scholar 

  9. Yang L, Zhang H, Zhang X, Tang Y, Wu Z, Wang Y, et al. Clinicopathologic and molecular features of denosumab-treated giant cell tumour of bone (GCTB): analysis of 21 cases. Ann Diagn Pathol. 2022;57: 151882. https://doi.org/10.1016/j.anndiagpath.2021.151882.

    Article  PubMed  Google Scholar 

  10. Li H, Gao J, Gao Y, Lin N, Zheng M, Ye Z. Denosumab in giant cell tumor of bone: current status and pitfalls. Front Oncol. 2020;10: 580605. https://doi.org/10.3389/fonc.2020.580605.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Lin X, Liu J, Xu M. The prognosis of giant cell tumor of bone and the vital risk factors that affect its postoperative recurrence: a meta-analysis. Transl Cancer Res. 2021;10(4):1712–22. https://doi.org/10.21037/tcr-20-3100.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Yang Y, Huang Z, Niu X, Xu H, Li Y, Liu W. Clinical characteristics and risk factors analysis of lung metastasis of benign giant cell tumor of bone. J Bone Oncol. 2017;7:23–8. https://doi.org/10.1016/j.jbo.2017.04.001.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Palmerini E, Picci P, Reichardt P, Downey G. Malignancy in giant cell tumor of bone: a review of the literature. Technol Cancer Res Treat. 2019;18:1533033819840000. https://doi.org/10.1177/1533033819840000.

    Article  PubMed  Google Scholar 

  14. Muheremu A, Niu X. Pulmonary metastasis of giant cell tumor of bones. World J Surg Oncol. 2014;12:261. https://doi.org/10.1186/1477-7819-12-261.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Aponte-Tinao LA, Piuzzi NS, Roitman P, Farfalli GL. A High-grade sarcoma arising in a patient with recurrent benign giant cell tumor of the proximal tibia while receiving treatment with denosumab. Clin Orthop Relat Res. 2015;473(9):3050–5. https://doi.org/10.1007/s11999-015-4249-2.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kondo T. Current status and future outlook for patient-derived cancer models from a rare cancer research perspective. Cancer Sci. 2021;112(3):953–61. https://doi.org/10.1111/cas.14669.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hattori E, Oyama R, Kondo T. Systematic review of the current status of human sarcoma cell lines. Cells. 2019;8(2):157. https://doi.org/10.3390/cells8020157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Goodspeed A, Heiser LM, Gray JW, Costello JC. Tumor-derived cell lines as molecular models of cancer pharmacogenomics. Mol Cancer Res. 2016;14(1):3–13. https://doi.org/10.1158/1541-7786.Mcr-15-0189.

    Article  CAS  PubMed  Google Scholar 

  19. Bairoch A. The cellosaurus, a cell-line knowledge resource. J Biomol Tech. 2018;29(2):25–38. https://doi.org/10.7171/jbt.18-2902-002.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Drexler HG, Dirks WG, MacLeod RA, Uphoff CC. False and mycoplasma-contaminated leukemia-lymphoma cell lines: time for a reappraisal. Int J Cancer. 2017;140(5):1209–14. https://doi.org/10.1002/ijc.30530.

    Article  CAS  PubMed  Google Scholar 

  21. Ono T, Noguchi R, Yoshimatsu Y, Tsuchiya R, Sin Y, Nakagawa R, et al. Establishment and characterization of the NCC-GCTB4-C1 cell line: a novel patient-derived cell line from giant cell tumor of bone. Hum Cell. 2022;35(1):392–9. https://doi.org/10.1007/s13577-021-00639-4.

    Article  CAS  PubMed  Google Scholar 

  22. Ono T, Noguchi R, Yoshimatsu Y, Sin Y, Tsuchiya R, Akiyama T, et al. Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone. Hum Cell. 2023;36(5):1804–12. https://doi.org/10.1007/s13577-023-00928-0.

    Article  CAS  PubMed  Google Scholar 

  23. Yoshimatsu Y, Noguchi R, Tsuchiya R, Ono T, Sin Y, Akane S, et al. Establishment and characterization of novel patient-derived cell lines from giant cell tumor of bone. Hum Cell. 2021;34(6):1899–910. https://doi.org/10.1007/s13577-021-00579-z.

    Article  CAS  PubMed  Google Scholar 

  24. Akiyama T, Yoshimatsu Y, Noguchi R, Sin Y, Tsuchiya R, Ono T, et al. Establishment and characterization of NCC-GCTB5-C1: a novel cell line of giant cell tumor of bone. Hum Cell. 2022;35(5):1621–9. https://doi.org/10.1007/s13577-022-00724-2.

    Article  CAS  PubMed  Google Scholar 

  25. Gonçalves E, Poulos RC, Cai Z, Barthorpe S, Manda SS, Lucas N, et al. Pan-cancer proteomic map of 949 human cell lines. Cancer Cell. 2022;40(8):835-49.e8. https://doi.org/10.1016/j.ccell.2022.06.010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kinker GS, Greenwald AC, Tal R, Orlova Z, Cuoco MS, McFarland JM, et al. Pan-cancer single-cell RNA-seq identifies recurring programs of cellular heterogeneity. Nat Genet. 2020;52(11):1208–18. https://doi.org/10.1038/s41588-020-00726-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Jiang G, Zhang S, Yazdanparast A, Li M, Pawar AV, Liu Y, et al. Comprehensive comparison of molecular portraits between cell lines and tumors in breast cancer. BMC Genomics. 2016;17(Suppl 7):525. https://doi.org/10.1186/s12864-016-2911-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Karpik M. Giant cell tumor (tumor gigantocellularis, osteoclastoma)—epidemiology, diagnosis, treatment. Ortop Traumatol Rehabil. 2010;12(3):207–15.

    PubMed  Google Scholar 

  29. Lim J, Park JH, Baude A, Yoo Y, Lee YK, Schmidt CR, et al. The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing. Sci Rep. 2017;7(1):13459. https://doi.org/10.1038/s41598-017-13887-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wang Y, Jeon H. 3D cell cultures toward quantitative high-throughput drug screening. Trends Pharmacol Sci. 2022;43(7):569–81. https://doi.org/10.1016/j.tips.2022.03.014.

    Article  CAS  PubMed  Google Scholar 

  31. Friedrich J, Seidel C, Ebner R, Kunz-Schughart LA. Spheroid-based drug screen: considerations and practical approach. Nat Protoc. 2009;4(3):309–24. https://doi.org/10.1038/nprot.2008.226.

    Article  CAS  PubMed  Google Scholar 

  32. Shimony S, Horowitz N, Ribakovsky E, Rozovski U, Avigdor A, Zloto K, et al. Romidepsin treatment for relapsed or refractory peripheral and cutaneous T-cell lymphoma: real-life data from a national multicenter observational study. Hematol Oncol. 2019;37(5):569–77. https://doi.org/10.1002/hon.2691.

    Article  CAS  PubMed  Google Scholar 

  33. Venneker S, van Eenige R, Kruisselbrink AB, Palubeckaitė I, Taliento AE, Briaire-de Bruijn IH, et al. Histone deacetylase inhibitors as a therapeutic strategy to eliminate neoplastic “stromal” cells from giant cell tumors of bone. Cancers (Basel). 2022;14(19):4708. https://doi.org/10.3390/cancers14194708.

    Article  CAS  PubMed  Google Scholar 

  34. Yafei J, Haoran M, Wenyan J, Linghang X, Kai T, Gangyang W, et al. Personalized medicine modality based on patient-derived xenografts from a malignant transformed GCTB harboring H3F3A G34W mutation. J Orthop Translat. 2021;29:106–12. https://doi.org/10.1016/j.jot.2021.04.004.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Evison BJ, Sleebs BE, Watson KG, Phillips DR, Cutts SM. Mitoxantrone, more than just another topoisomerase II poison. Med Res Rev. 2016;36(2):248–99. https://doi.org/10.1002/med.21364.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Drs. S. Fukushima, S. Osaki, S. Iwata (Department of Musculoskeletal Oncology and Rehabilitation), and Y. Takahashi (Department of Diagnostic Pathology), and the National Cancer Center Hospital for sampling the tumor tissue specimens from surgically resected materials. We appreciate the technical assistance provided by Mr. Y. Ohno (Division of Rare Cancer Research, National Cancer Center Research Institute) and Mrs. Y. Shiotani (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 the manuscript. Technical assistance for this study was provided by the Fundamental Innovative Oncology Core of the National Cancer Center.

Funding

This study was supported by the Japan Agency for Medical Research and Development (Grant Number: 20ck0106537h).

Author information

Author notes

  1. Yuki Yoshimatsu

    Present address: Department of Patient-Derived Cancer Model, Tochigi Cancer Center, 4-9-13 Yohnan, Utsunomiya, Tochigi, 320-0834, Japan

  2. Taro Akiyama & Ryuto Tsuchiya

    Present address: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, 260-8670, Japan

Authors and Affiliations

  1. Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Yuki Adachi, Rei Noguchi, Yuki Yoshimatsu, Yooksil Sin, Julia Osaki, Takuya Ono, Shuhei Iwata, Taro Akiyama, Ryuto Tsuchiya & Tadashi Kondo

  2. Division of Hepato-Biliary-Pancreatic Surgery and Transplant Surgery, Department of Surgery, Asahikawa Medical University, 2-1-1 Midorigaoka Higashi, Asahikawa, Hokkaido, Japan

    Yuki Adachi & Hideki Yokoo

  3. Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Yu Toda, Shin Ishihara, Koichi Ogura, Eisuke Kobayashi & Akira Kawai

  4. Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Naoki Kojima & Akihiko Yoshida

Authors
  1. Yuki Adachi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rei Noguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuki Yoshimatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yooksil Sin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Julia Osaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takuya Ono
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shuhei Iwata
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Taro Akiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ryuto Tsuchiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yu Toda
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Shin Ishihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Koichi Ogura
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Eisuke Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Naoki Kojima
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Akihiko Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Hideki Yokoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Akira Kawai
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Tadashi Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tadashi Kondo.

Ethics declarations

Conflicts of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

The use of clinical materials for this study was approved by the ethics committee of the National Cancer Center (approval number: 2004-050).

Informed consent

Written informed consent was provided by the patients.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Adachi, Y., Noguchi, R., Yoshimatsu, Y. et al. Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone: NCC-GCTB8-C1 and NCC-GCTB9-C1. Human Cell 37, 874–885 (2024). https://doi.org/10.1007/s13577-024-01042-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-024-01042-5

Keywords

Search

Navigation