Abstract
Giant cell tumor of bone (GCTB) is a rare osteolytic bone tumor, accounting for approximately 5% of all primary bone tumors. GCTB is characterized by unique giant cells. It is also characterized by recurrent mutations in the histone tail of the histone variant H3.3, H3F3A, on chromosome 1, therapeutic implications of which have not been established yet. There are few effective standardized treatments for GCTB, and a novel therapy has long been required. Patient-derived cancer cells have facilitated the understanding of mechanisms underlying the etiology and progression of multiple cancers. Thus far, only 10 GCTB cell lines have been reported, and none of them are publicly available. The aim of this study was to develop an accessible patient-derived cell line of GCTB, which could be used as a screening tool for drug development. Here, we describe the establishment of a cell line, designated NCC-GCTB1-C1, from the primary tumor tissue of a male patient with GCTB on the right distal radius. NCC-GCTB1-C1 cells were maintained as a monolayer culture for over 23 passages for 7 months. These cells exhibited continuous growth, as well as spheroid formation and invasive ability. Using an oncology agent screen, we tested the effect of anticancer drugs on the proliferation of NCC-GCTB1-C1 cells. The cells displayed a remarkable response to romidepsin and vincristine. Thus, we established a novel GCTB cell line, NCC-GCTB1-C1, which could be a useful tool for studying GCTB tumorigenesis and the efficacy of anticancer drugs.
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Acknowledgements
We appreciate the technical support provided by Miss Yu Kuwata (Division of Rare Cancer Research, National Cancer Center). We would like to thank the Tochigi Cancer Center Operating Room Nurse Team and the Secretary of the Medical Office for their assistance in processing and transporting the samples. We would like to thank Editage (https://www.editage.jp) for providing English-language editing service and for their constructive comments on the manuscript.
Funding
This research was supported by the Japan Agency for Medical Research and Development Grant (20ck0106537h0001), titled “Study to Overcome the Limits of Cancer Genome-based Medicine Using Patient-derived ‘Rare Cancer’ Model”.
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This study was approved by the ethics committee of the Tochigi Cancer Center and the National Cancer Center, and written informed consent was obtained from the patient.
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Supplementary Figure 1 Single tandem repeat patterns in sequencing data from the original tumor and NCC-GCTB1-C1 cells (TIF 307 kb)
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Supplementary Figure 2 Images of invading NCC-GCTB1-C1 cells on the membrane of the upper chamber in transwell assays (TIF 535 kb)
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Supplementary Figure 3 Growth curves of agents that showed relatively higher inhibition of NCC-GCTB1-C1 cell proliferation (TIF 753 kb)
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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. Human Cell 33, 1321–1328 (2020). https://doi.org/10.1007/s13577-020-00415-w
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DOI: https://doi.org/10.1007/s13577-020-00415-w