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Establishment and characterization of NCC-ssRMS2-C1: a novel patient-derived cell line of spindle cell/sclerosing rhabdomyosarcoma

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Abstract

Spindle cell/sclerosing rhabdomyosarcoma (ssRMS) is a rare subtype of rhabdomyosarcoma (RMS) that has fascicular spindle cell and/or sclerosing morphology. SsRMS has a diverse molecular background and is categorized into three groups: congenital/infantile ssRMS with a gene fusion involving the NCOA2 and VGLL2, ssRMS with the MYOD1 mutation, and ssRMS with no recurrent identifiable genetic alterations. Because ssRMS is a newly defined disease concept of RMS, the optimal treatment methods have not been determined. This results in unfavorable prognosis and consequently signals the urgent need for continuous research. Patient-derived cell lines are essential tools in basic and translational research. However, only two ssRMS cell lines with the MYOD1 mutation have been reported to date. Thus, we established a novel ssRMS cell line named NCC-ssRMS2-C1 using a surgically resected tumor tissue from an adult ssRMS patient. NCC-ssRMS2-C1 cells retained the copy number alterations corresponding to the original tumor and are categorized into the group with no recurrent identifiable genetic alterations. NCC-ssRMS2-C1 cells demonstrated constant proliferation, spheroid formation, and capability for invasion in vitro, reflecting the malignant features of the original tumor tissue. In a drug screening test, ssRMS demonstrated remarkable sensitivity to romidepsin, trabectedin, actinomycin D, and bortezomib. Hence, we conclude that the NCC-ssRMS2-C1 cell line is the first ssRMS cell line which belongs to the group with no recurrent identifiable genetic alterations, and it will be a useful resource in both basic and translational studies for ssRMS.

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Acknowledgements

We thank Drs. E. Kobayashi, S. Iwata, S. Fukushima, M. Nakagawa, T. Komatsubara, C. Sato (Department of Musculoskeletal Oncology), and Drs. N. Kojima, J. Kashima, M. Arakaki (Department of Diagnostic Pathology), National Cancer Center Hospital, for sampling tumor tissue specimens from surgically resected materials. We also appreciate the technical assistance provided by Ms. Y. Kuwata (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 in the National Cancer Center.

Funding

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

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Authors and Affiliations

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

    Ryuto Tsuchiya, Yuki Yoshimatsu, Rei Noguchi, Yooksil Sin, Takuya Ono, Akane Sei & Tadashi Kondo

  2. Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan

    Ryuto Tsuchiya & Seiji Ohtori

  3. Department of Translational Oncology, Fundamental Innovative Oncology Core Center, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Fumitaka Takeshita

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

    Jun Sugaya, Fumihiko Nakatani & Akira Kawai

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

    Akihiko Yoshida

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  1. Ryuto Tsuchiya
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  2. Yuki Yoshimatsu
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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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Written informed consent for publication was provided by the patient.

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Tsuchiya, R., Yoshimatsu, Y., Noguchi, R. et al. Establishment and characterization of NCC-ssRMS2-C1: a novel patient-derived cell line of spindle cell/sclerosing rhabdomyosarcoma. Human Cell 34, 1569–1578 (2021). https://doi.org/10.1007/s13577-021-00569-1

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  • DOI: https://doi.org/10.1007/s13577-021-00569-1

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