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

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Abstract

Giant cell tumor of bone (GCTB) is a rare bone tumor with osteolytic features, composed of stromal cells with a monotonous appearance, macrophages, and osteoclast-like giant cells. GCTB is commonly associated with a pathogenic mutation in the H3-3A gene. While complete surgical resection is the standard cure for GCTB, it often results in local recurrence and, rarely, metastasis. Thus, an effective multidisciplinary treatment approach is necessary. Although patient-derived cell lines is an essential tool for investigating novel treatment strategies, there are only four GCTB cell lines available in public cell banks. Therefore, this study aimed to establish novel GCTB cell lines and successfully created NCC-GCTB6-C1 and NCC-GCTB7-C1 cell lines from two patients' surgically removed tumor tissues. These cell lines exhibited H3-3A gene mutations, consistent proliferation, and invasive properties. After characterizing their behaviors, we performed high-throughput screening of 214 anti-cancer drugs for NCC-GCTB6-C1 and NCC-GCTB7-C1 and integrated their screening data with those of NCC-GCTB1-C1, NCC-GCTB2-C1, NCC-GCTB3-C1, NCC-GCTB4-C1, and NCC-GCTB5-C1 that we previously established. We identified histone deacetylase inhibitor romidepsin as a possible treatment for GCTB. These findings suggest that NCC-GCTB6-C1 and NCC-GCTB7-C1 could be valuable tools for preclinical and basic research on GCTB.

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Acknowledgements

We thank Drs. E. Kobayashi, S. Iwata, K. Ogura, K. Sato (Department of Musculoskeletal Oncology), Dr. Y. Takahashi (Department of Diagnostic Pathology), and the National Cancer Center Hospital for sampling tumor tissue specimens from surgically resected materials. We appreciate the 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.

Funding

This research was supported by the Japan Agency for Medical Research and Development (Grant number: 20ck0106537h0003).

Author information

Author notes

  1. Yuki Yoshimatsu

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

  2. Ryuto Tsuchiya & Taro Akiyama

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

    Takuya Ono, Rei Noguchi, Yuki Yoshimatsu, Yooksil Sin, Ryuto Tsuchiya, Taro Akiyama & Tadashi Kondo

  2. Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan

    Takuya Ono

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

    Naoki Kojima & Akihiko Yoshida

  4. Division of Musculoskeletal Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Yu Toda, Chiaki Sato, Suguru Fukushima & Akira Kawai

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  1. Takuya Ono
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Correspondence to Tadashi Kondo.

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The authors declare that they have no conflicts of interest.

Ethics approval

The ethical committee of the National Cancer Center (Tokyo, Japan) 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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Written informed consent was provided by the patients.

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Supplementary Information

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13577_2023_928_MOESM1_ESM.tif

Supplementary file1 Supplementary Fig. 1 Short tandem repeat patterns of GCTB cell lines and original tumor tissues. (a) Short tandem repeat patterns of NCC-GCTB6-C1 (passage 20), (b) Short tandem repeat patterns of original tumor tissue of NCC-GCTB6-C1, (c) Short tandem repeat patterns of NCC-GCTB7-C1 (passage 20), (d) Short tandem repeat patterns of original tumor tissue of NCC-GCTB7-C1 (TIF 517 KB)

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Ono, T., Noguchi, R., Yoshimatsu, Y. et al. Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone. Human Cell 36, 1804–1812 (2023). https://doi.org/10.1007/s13577-023-00928-0

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