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Establishment and characterization of novel patient-derived cell lines from giant cell tumor of bone

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Abstract

Giant cell tumor of bone (GCTB) is a locally aggressive and rarely metastasizing tumor. GCTB is characterized by the presence of unique giant cells and a recurrent mutation in the histone tail of the histone variant H3.3, which is encoded by H3F3A on chromosome 1. GCTB accounts for ~ 5% of primary bone tumors. Although GCTB exhibits an indolent course, it has the potential to develop aggressive behaviors associated with local recurrence and distant metastasis. Currently, complete surgical resection is the only curative treatment, and novel therapeutic strategies are required. Patient-derived cancer cell lines are critical tools for basic and pre-clinical research. However, only a few GCTB cell lines have been reported, and none of them are available from public cell banks. Therefore, we aimed to establish novel GCTB cell lines in the present study. Using curetted tumor tissues of GCTB, we established two cell lines and named them NCC-GCTB2-C1 and NCC-GCTB3-C1. These cells harbored a typical mutation in histones and exhibited slow but constant growth, formed spheroids, and had invasive capabilities. We demonstrated the utility of these cell lines for high-throughput drug screening using 214 anticancer agents. We concluded that NCC-GCTB2-C1 and NCC-GCTB3-C1 cell lines were useful for the in vitro study of GCTB.

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References

  1. Liede A, Bach BA, Stryker S, et al. Regional variation and challenges in estimating the incidence of giant cell tumor of bone. J Bone Joint Surg Am. 2014;96:1999–2007.

    Article  PubMed  Google Scholar 

  2. Behjati S, Tarpey PS, Presneau N, et al. Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone. Nat Genet. 2013;45:1479–82.

    Article  CAS  PubMed  Google Scholar 

  3. Presneau N, Baumhoer D, Behjati S, et al. Diagnostic value of H3F3A mutations in giant cell tumour of bone compared to osteoclast-rich mimics. J Pathol Clin Res. 2015;1:113–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Cleven AH, Höcker S, Briaire-de Bruijn I, Szuhai K, Cleton-Jansen AM, Bovée JV. Mutation analysis of H3F3A and H3F3B as a diagnostic tool for giant cell tumor of bone and chondroblastoma. Am J Surg Pathol. 2015;39:1576–83.

    Article  PubMed  Google Scholar 

  5. Eckardt JJ, Grogan TJ. Giant cell tumor of bone. Clin Orthop Relat Res. 1986. https://doi.org/10.1097/00003086-198603000-00006.

    Article  PubMed  Google Scholar 

  6. McGrath PJ. Giant-cell tumour of bone: an analysis of fifty-two cases. J Bone Joint Surg Br Vol. 1972;54:216–29.

    Article  CAS  Google Scholar 

  7. Bridge JA, Neff JR, Mouron BJ. Giant cell tumor of bone. Chromosomal analysis of 48 specimens and review of the literature. Cancer Genet Cytogenet. 1992;58:2–13.

    Article  CAS  PubMed  Google Scholar 

  8. Harness NG, Mankin HJ. Giant-cell tumor of the distal forearm. J Hand Surg. 2004;29:188–93.

    Article  Google Scholar 

  9. Moon JC, Kim SR, Lee YC, Chung MJ. Multiple pulmonary metastases from giant cell tumor of a hand. Am J Med Sci. 2012;343:171–3.

    Article  PubMed  Google Scholar 

  10. Errani C, Ruggieri P, Asenzio MA, et al. Giant cell tumor of the extremity: A review of 349 cases from a single institution. Cancer Treat Rev. 2010;36:1–7.

    Article  PubMed  Google Scholar 

  11. Balke M, Schremper L, Gebert C, et al. Giant cell tumor of bone: treatment and outcome of 214 cases. J Cancer Res Clin Oncol. 2008;134:969–78.

    Article  CAS  PubMed  Google Scholar 

  12. Becker WT, Dohle J, Bernd L, et al. Local recurrence of giant cell tumor of bone after intralesional treatment with and without adjuvant therapy. J Bone Joint Surg Am. 2008;90:1060–7.

    Article  PubMed  Google Scholar 

  13. Kivioja AH, Blomqvist C, Hietaniemi K, et al. Cement is recommended in intralesional surgery of giant cell tumors: a Scandinavian Sarcoma Group study of 294 patients followed for a median time of 5 years. Acta Orthop. 2008;79:86–93.

    Article  PubMed  Google Scholar 

  14. Algawahmed H, Turcotte R, Farrokhyar F, Ghert M. High-speed burring with and without the use of surgical adjuvants in the intralesional management of giant cell tumor of bone: a systematic review and meta-analysis. Sarcoma. 2010;2010:1–5.

    Article  Google Scholar 

  15. Chan CM, Adler Z, Reith JD, Gibbs CP Jr. Risk factors for pulmonary metastases from giant cell tumor of bone. J Bone Joint Surg Am. 2015;97:420–8.

    Article  PubMed  Google Scholar 

  16. Dominkus M, Ruggieri P, Bertoni F, et al. Histologically verified lung metastases in benign giant cell tumours–14 cases from a single institution. Int Orthop. 2006;30:499–504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wang J, Liu X, Yang Y, et al. Pulmonary metastasis of giant cell tumour: a retrospective study of three hundred and ten cases. Int Orthop. 2021;45:769–78.

    Article  PubMed  Google Scholar 

  18. Huang L, Xu J, Wood DJ, Zheng MH. Gene expression of osteoprotegerin ligand, osteoprotegerin, and receptor activator of NF-kappaB in giant cell tumor of bone: possible involvement in tumor cell-induced osteoclast-like cell formation. Am J Pathol. 2000;156:761–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Atkins GJ, Bouralexis S, Haynes DR, et al. Osteoprotegerin inhibits osteoclast formation and bone resorbing activity in giant cell tumors of bone. Bone. 2001;28:370–7.

    Article  CAS  PubMed  Google Scholar 

  20. Branstetter DG, Nelson SD, Manivel JC, et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012;18:4415–24.

    Article  CAS  PubMed  Google Scholar 

  21. Kostenuik PJ, Nguyen HQ, McCabe J, et al. Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL. J Bone Mineral Res. 2009;24:182–95.

    Article  CAS  Google Scholar 

  22. Chawla S, Henshaw R, Seeger L, et al. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol. 2013;14:901–8.

    Article  CAS  PubMed  Google Scholar 

  23. Thomas D, Henshaw R, Skubitz K, et al. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010;11:275–80.

    Article  CAS  PubMed  Google Scholar 

  24. Errani C, Tsukamoto S, Leone G, et al. Denosumab may increase the risk of local recurrence in patients with giant-cell tumor of bone treated with curettage. J Bone Joint Surg Am. 2018;100:496–504.

    Article  PubMed  Google Scholar 

  25. Scoccianti G, Totti F, Scorianz M, et al. Preoperative denosumab with curettage and cryotherapy in giant cell tumor of bone: Is there an increased risk of local recurrence? Clin Orthop Relat Res. 2018;476:1783–90.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Sano K, Suehara Y, Okubo T, et al. Preoperative denosumab treatment with curettage may be a risk factor for recurrence of giant cell tumor of bone. J Orthop Surg (Hong Kong). 2020;28:2309499020929786.

    Article  Google Scholar 

  27. Boriani S, Sudanese A, Baldini N, Picci P. Sarcomatous degeneration of giant cell tumours. Ital J Orthop Traumatol. 1986;12:191–9.

    CAS  PubMed  Google Scholar 

  28. Lipplaa A, Dijkstra S, Gelderblom H. Challenges of denosumab in giant cell tumor of bone, and other giant cell-rich tumors of bone. Curr Opin Oncol. 2019;31:329–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sharma SV, Haber DA, Settleman J. Cell line-based platforms to evaluate the therapeutic efficacy of candidate anticancer agents. Nat Rev Cancer. 2010;10:241–53.

    Article  CAS  PubMed  Google Scholar 

  30. Lim J, Park JH, Baude A, et al. The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing. Sci Rep. 2017;7:13459.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Fellenberg J, Sähr H, Mancarella D, et al. Knock-down of oncohistone H3F3A-G34W counteracts the neoplastic phenotype of giant cell tumor of bone derived stromal cells. Cancer Lett. 2019;448:61–9.

    Article  CAS  PubMed  Google Scholar 

  32. Barretina J, Caponigro G, Stransky N, et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012;483:603–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Garnett MJ, Edelman EJ, Heidorn SJ, et al. Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature. 2012;483:570–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Basu A, Bodycombe NE, Cheah JH, et al. An interactive resource to identify cancer genetic and lineage dependencies targeted by small molecules. Cell. 2013;154:1151–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Seashore-Ludlow B, Rees MG, Cheah JH, et al. Harnessing connectivity in a large-scale small-molecule sensitivity dataset. Cancer Discov. 2015;5:1210–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Rees MG, Seashore-Ludlow B, Cheah JH, et al. Correlating chemical sensitivity and basal gene expression reveals mechanism of action. Nat Chem Biol. 2016;12:109–16.

    Article  CAS  PubMed  Google Scholar 

  37. Haverty PM, Lin E, Tan J, et al. Reproducible pharmacogenomic profiling of cancer cell line panels. Nature. 2016;533:333–7.

    Article  CAS  PubMed  Google Scholar 

  38. Iorio F, Knijnenburg TA, Vis DJ, et al. A landscape of pharmacogenomic interactions in cancer. Cell. 2016;166:740–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Behan FM, Iorio F, Picco G, et al. Prioritization of cancer therapeutic targets using CRISPR-Cas9 screens. Nature. 2019;568:511–6.

    Article  CAS  PubMed  Google Scholar 

  40. Townsend EC, Murakami MA, Christodoulou A, et al. The public repository of xenografts enables discovery and randomized phase II-like trials in mice. Cancer Cell. 2016;29:574–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Bairoch A. The Cellosaurus, a cell-Line knowledge resource. J Biomol Tech. 2018;29:25–38.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Noguchi R, Yoshimatsu Y, Ono T, 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;33:1321–8.

    Article  CAS  PubMed  Google Scholar 

  43. Capes-Davis A, Reid YA, Kline MC, et al. Match criteria for human cell line authentication: where do we draw the line? Int J Cancer. 2013;132:2510–9.

    Article  CAS  PubMed  Google Scholar 

  44. Turcotte RE. Giant cell tumor of bone. Orthop Clin North Am. 2006;37:35–51.

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  46. Niu X, Zhang Q, Hao L, et al. Giant cell tumor of the extremity: retrospective analysis of 621 Chinese patients from one institution. J Bone Joint Surg Am. 2012;94:461–7.

    Article  PubMed  Google Scholar 

  47. Prince HM, Dickinson M. Romidepsin for cutaneous T-cell lymphoma. Clin Cancer Res. 2012;18:3509–15.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We appreciate the technical support provided by Mesdames Yu Kuwata and Rina Sasaki (Division of Rare Cancer Research, National Cancer Center). We would like to thank Drs. F Nakatani, S. Iwata, E Kobayashi, M Nakagawa, T Komatsubara, M Saito, C Sato (Department of Musculoskeletal Oncology, National Cancer Center Hospital), Drs. T Shibayama, and H Tanaka (Department of Diagnostic Pathology, National Cancer Center Hospital) for sampling tumor tissue specimens from curetted materials. (Division of Rare Cancer Research). We appreciate the technical support provided by Ms. Y Shiotani, Mr. N Uchiya, and Dr. T Imai (Central Animal Division, National Cancer Center Research Institute). We would also like to thank Editage (www.editage.jp) for their help with English language editing and their constructive comments on the manuscript. This research was technically assisted by the Fundamental Innovative Oncology Core at the National Cancer Center This research was supported by the Japan Agency for Medical Research and Development (Grant number 20ck0106537h0001).

Funding

This research was supported by the Japan Agency for Medical Research and Development (Grant number 20ck0106537h0001).

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Correspondence to Tadashi Kondo.

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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).

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Yoshimatsu, Y., Noguchi, R., Tsuchiya, R. et al. Establishment and characterization of novel patient-derived cell lines from giant cell tumor of bone. Human Cell 34, 1899–1910 (2021). https://doi.org/10.1007/s13577-021-00579-z

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  • DOI: https://doi.org/10.1007/s13577-021-00579-z

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