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Establishment and characterization of NCC-MFS2-C1: a novel patient-derived cancer cell line of myxofibrosarcoma

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Abstract

Myxofibrosarcoma (MFS) is among the most aggressive and complex sarcoma types that require novel therapeutic approaches for improved clinical outcomes. MFS displays highly complex karyotypes, and frequent alterations in p53 signaling and cell cycle checkpoint genes as well as loss-of-function mutations in NF1 and PTEN have been reported. The effects of radiotherapy and chemotherapy on MFS are limited, and complete surgical resection is the only curative treatment. Thus, the development of novel therapeutic strategies for MFS has long been long desired for MFS. Patient-derived cell lines are an essential tool for basic and translational research in oncology. However, public cell banks provide only a limited number of MFS cell lines. In this study, we aimed to develop a novel patient-derived MFS cell line, which was established from the primary tumor tissue of a 71-year-old male patient with MFS and was named NCC-MFS2-C1. A single-nucleotide polymorphism assay revealed that NCC-MFS2-C1 cells exhibited gain and loss of genetic loci. NCC-MFS2-C1 cells were maintained as a monolayer culture for over 24 passages for 10 months. The cells exhibited spindle-like morphology, continuous growth, and capacity for spheroid formation and invasion. Screening of 213 anticancer agents revealed that bortezomib, gemcitabine, romidepsin, and topotecan at low concentrations inhibited the proliferation of NCC-MFS2-C1 cells. In conclusion, we established a novel MFS cell line, NCC-MFS2-C1, which can be used for studying the molecular mechanisms underlying tumor development and for the in vitro screening of anti-cancer drugs.

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Acknowledgements

We appreciate the technical support by Miss Yu Kuwata (Division of Rare Cancer Research, National Cancer Center). We would also 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. The Fundamental Innovative Oncology Core at the National Cancer Center provided support for the SNParray experiment. We would like to thank Editage (www.editage.jp) for English editing and constructive comments on the manuscript.

Funding

This research was supported by the Japan Agency for Medical Research and Development grant 20ck0106537h0001, “Study to Overcome the Limits of Cancer Genome-based Medicine Using Patient-derived “Rare Cancer” Model”.

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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

    Rei Noguchi, Yuki Yoshimatsu, Takuya Ono, Akane Sei & Tadashi Kondo

  2. Division of Diagnostic Pathology, Tochigi Cancer Center, 4-9-13 Yohnan, Utsunomiya, Tochigi, 320-0834, Japan

    Kaoru Hirabayashi & Tadashi Kondo

  3. Division of Hepato-Biliary-Pancreatic Surgery, Tochigi Cancer Center, 4-9-13 Yohnan, Utsunomiya, Tochigi, 320-0834, Japan

    Iwao Ozawa

  4. Division of Musculoskeletal Oncology and Orthopaedics Surgery, Tochigi Cancer Center, 4-9-13 Yohnan, Utsunomiya, Tochigi, 320-0834, Japan

    Kazutaka Kikuta

Authors
  1. Rei Noguchi
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  2. Yuki Yoshimatsu
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  3. Takuya Ono
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  4. Akane Sei
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  5. Kaoru Hirabayashi
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  6. Iwao Ozawa
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  7. Kazutaka Kikuta
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  8. Tadashi Kondo
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Corresponding author

Correspondence to Tadashi Kondo.

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The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. 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 of the original tumor and NCC-MFS2-C1 cells (TIF 209 kb)

Supplementary Figure 2 Images of invading NCC-MFS2-C1 cells on the membrane of the upper chamber (TIF 671 kb)

13577_2020_420_MOESM3_ESM.tif

Supplementary Figure 3 Growth curves with agents that showed relatively higher inhibitory effects on NCC-MFS2-C1 cell proliferation (TIF 689 kb)

Supplementary Table 1 List of 213 anti-cancer agents examined in this study (XLSX 24 kb)

Supplementary Table 2 Cell viability after treatment with anti-cancer drugs (%) (XLSX 49 kb)

13577_2020_420_MOESM6_ESM.xlsx

Supplementary Table 3 IC50 values of four agents that showed high inhibitory effects on NCC-MFS2-C1 cell proliferation (XLSX 11 kb)

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Noguchi, R., Yoshimatsu, Y., Ono, T. et al. Establishment and characterization of NCC-MFS2-C1: a novel patient-derived cancer cell line of myxofibrosarcoma. Human Cell 34, 246–253 (2021). https://doi.org/10.1007/s13577-020-00420-z

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  • DOI: https://doi.org/10.1007/s13577-020-00420-z

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