Skip to main content

Advertisement

SpringerLink
Log in

Establishment and characterization of NCC-UPS3-C1: a novel patient-derived cell line of undifferentiated pleomorphic sarcoma

  • Cell Line
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

Undifferentiated pleomorphic sarcoma (UPS), previously termed malignant fibrous histiocytoma, is one of the most aggressive sarcomas with no identifiable line of differentiation. Although the molecular mechanism of oncogenesis in UPS has not been clarified, radiation exposure is considered to be a risk factor in the development of UPS. In the treatment of UPS, surgical treatment remains the most important modality. While chemotherapy is considered in unresectable or metastatic cases, UPS is known to be refractory to conventional chemotherapy, leading to an unfavorable prognosis. To improve the clinical outcome of this condition, novel treatment methods are urgently needed. Patient-derived cell lines are essential tools in preclinical studies. However, owing to the rarity of UPS, only four UPS cell lines are publicly available. Thus, we established a novel UPS cell line, NCC-UPS3-C1, using a surgically resected tumor from a patient with radiation-associated UPS. NCC-UPS3-C1 cells had multiple genomic deletions including the tumor suppressor genes CDKN2A and CDKN2B. NCC-UPS3-C1 cells demonstrated constant growth, spheroid formation, and aggressive invasion ability. We also conducted a screening test using 214 drugs and identified that the histone deacetylase inhibitor, romidepsin, is highly effective on NCC-UPS3-C1 cells. Thus, we concluded that the NCC-UPS3-C1 cell line is a useful tool in preclinical studies for UPS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. WHO classification of tumours of soft tissue and bone. 5th edn. Lyon: IARC; 2020.

  2. Widemann BC, Italiano A. Biology and management of undifferentiated pleomorphic sarcoma, myxofibrosarcoma, and malignant peripheral nerve sheath tumors: state of the art and perspectives. J Clin Oncol. 2018;36:160–7.

    Article  CAS  Google Scholar 

  3. Chen S, Huang W, Luo P, et al. Undifferentiated pleomorphic sarcoma: long-term follow-up from a large institution. Cancer Manag Res. 2019;11:10001–9.

    Article  Google Scholar 

  4. Gladdy RA, Qin LX, Moraco N, et al. Do radiation-associated soft tissue sarcomas have the same prognosis as sporadic soft tissue sarcomas? J Clin Oncol. 2010;28:2064–9.

    Article  Google Scholar 

  5. Dineen SP, Roland CL, Feig R, et al. Radiation-associated undifferentiated pleomorphic sarcoma is associated with worse clinical outcomes than sporadic lesions. Ann Surg Oncol. 2015;22:3913–20.

    Article  Google Scholar 

  6. Joo MW, Kang YK, Ogura K, et al. Post-radiation sarcoma: a study by the Eastern Asian Musculoskeletal Oncology Group. PLoS ONE. 2018;13:e0204927.

    Article  Google Scholar 

  7. Callesen LB, Safwat A, Rose HK, Sorensen FB, Baad-Hansen T, Aggerholm-Pedersen N. Radiation-induced sarcoma: a retrospective population-based study over 34 years in a single institution. Clin Oncol (R Coll Radiol). 2021;33:e232–8.

    Article  CAS  Google Scholar 

  8. Vodanovich DA, Spelman T, May D, Slavin J, Choong PFM. Predicting the prognosis of undifferentiated pleomorphic soft tissue sarcoma: a 20-year experience of 266 cases. ANZ J Surg. 2019;89:1045–50.

    Article  Google Scholar 

  9. Kresse SH, Ohnstad HO, Bjerkehagen B, Myklebost O, Meza-Zepeda LA. DNA copy number changes in human malignant fibrous histiocytomas by array comparative genomic hybridisation. PLoS ONE. 2010;5:e15378.

    Article  Google Scholar 

  10. Carneiro A, Francis P, Bendahl PO, et al. Indistinguishable genomic profiles and shared prognostic markers in undifferentiated pleomorphic sarcoma and leiomyosarcoma: different sides of a single coin? Lab Invest. 2009;89:668–75.

    Article  CAS  Google Scholar 

  11. Simons A, Schepens M, Jeuken J, et al. Frequent loss of 9p21 (p16(INK4A)) and other genomic imbalances in human malignant fibrous histiocytoma. Cancer Genet Cytogenet. 2000;118:89–98.

    Article  CAS  Google Scholar 

  12. Perot G, Chibon F, Montero A, et al. Constant p53 pathway inactivation in a large series of soft tissue sarcomas with complex genetics. Am J Pathol. 2010;177:2080–90.

    Article  CAS  Google Scholar 

  13. Gibault L, Perot G, Chibon F, et al. New insights in sarcoma oncogenesis: a comprehensive analysis of a large series of 160 soft tissue sarcomas with complex genomics. J Pathol. 2011;223:64–71.

    Article  CAS  Google Scholar 

  14. Kamat NV, Million L, Yao DH, et al. The outcome of patients with localized undifferentiated pleomorphic sarcoma of the lower extremity treated at Stanford University. Am J Clin Oncol. 2019;42:166–71.

    Article  Google Scholar 

  15. Goldblum JR. An approach to pleomorphic sarcomas: can we subclassify, and does it matter? Mod Pathol. 2014;27(Suppl 1):S39-46.

    Article  Google Scholar 

  16. Grimer R, Judson I, Peake D, Seddon B. Guidelines for the management of soft tissue sarcomas. Sarcoma. 2010;2010:506182.

    PubMed  PubMed Central  Google Scholar 

  17. Reichardt P. Soft tissue sarcomas, a look into the future: different treatments for different subtypes. Future Oncol. 2014;10:s19-27.

    Article  CAS  Google Scholar 

  18. Saito S, Morita K, Kohara A, et al. Use of BAC array CGH for evaluation of chromosomal stability of clinically used human mesenchymal stem cells and of cancer cell lines. Hum Cell. 2011;24:2–8.

    Article  Google Scholar 

  19. Ben-David U, Beroukhim R, Golub TR. Genomic evolution of cancer models: perils and opportunities. Nat Rev Cancer. 2019;19:97–109.

    Article  CAS  Google Scholar 

  20. 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  Google Scholar 

  21. 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  Google Scholar 

  22. Shoemaker RH. The NCI60 human tumour cell line anticancer drug screen. Nat Rev Cancer. 2006;6:813–23.

    Article  CAS  Google Scholar 

  23. Yang W, Soares J, Greninger P, et al. Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells. Nucleic Acids Res. 2013;41:D955–61.

    Article  CAS  Google Scholar 

  24. Goodspeed A, Heiser LM, Gray JW, Costello JC. Tumor-derived cell lines as molecular models of cancer pharmacogenomics. Mol Cancer Res. 2016;14:3–13.

    Article  CAS  Google Scholar 

  25. Hattori E, Oyama R, Kondo T. Systematic review of the current status of human sarcoma cell lines. Cells. 2019;8:157.

    Article  CAS  Google Scholar 

  26. Bairoch A. The cellosaurus, a cell-line knowledge resource. J Biomol Tech. 2018;29:25–38.

    Article  Google Scholar 

  27. Amm HM, DeVilliers P, Srivastava AR, Diniz MG, Siegal GP, MacDougall M. Mandibular undifferentiated pleomorphic sarcoma: molecular analysis of a primary cell population. Clin Exp Dent Res. 2020;6:495–505.

    Article  Google Scholar 

  28. De Vita A, Recine F, Mercatali L, et al. Primary culture of undifferentiated pleomorphic sarcoma: molecular characterization and response to anticancer agents. Int J Mol Sci. 2017;18:2662.

    Article  Google Scholar 

  29. Tsuchiya R, Yoshimatsu Y, Noguchi R, et al. Establishment and characterization of NCC-SS4-C1: a novel patient-derived cell line of synovial sarcoma. Hum Cell. 2021;34:998–1007.

    Article  CAS  Google Scholar 

  30. Sin Y, Yoshimatsu Y, Noguchi R, et al. Establishment and characterization of a novel alveolar rhabdomyosarcoma cell line, NCC-aRMS1-C1. Hum Cell. 2020;33:1311–20.

    Article  CAS  Google Scholar 

  31. Billiau A, Edy VG, Heremans H, et al. Human interferon: mass production in a newly established cell line, MG-63. Antimicrob Agents Chemother. 1977;12:11–5.

    Article  CAS  Google Scholar 

  32. Tanabe H, Takada Y, Minegishi D, Kurematsu M, Masui T, Mizusawa H. Cell line individualization by STR multiplex system in the cell bank found cross-contamination between ECV304 and EJ-1/T24. Tiss Cult Res Commun. 1999;18:329–38.

    Google Scholar 

  33. 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  Google Scholar 

  34. Bui NQ, Przybyl J, Trabucco SE, et al. A clinico-genomic analysis of soft tissue sarcoma patients reveals CDKN2A deletion as a biomarker for poor prognosis. Clin Sarcoma Res. 2019;9:12.

    Article  Google Scholar 

  35. Orth MF, Gerke JS, Knosel T, et al. Functional genomics identifies AMPD2 as a new prognostic marker for undifferentiated pleomorphic sarcoma. Int J Cancer. 2019;144:859–67.

    Article  CAS  Google Scholar 

  36. De Vita A, Recine F, Miserocchi G, et al. The potential role of the extracellular matrix in the activity of trabectedin in UPS and L-sarcoma: evidences from a patient-derived primary culture case series in tridimensional and zebrafish models. J Exp Clin Cancer Res. 2021;40:165.

    Article  Google Scholar 

  37. Takai Y, Oyama R, Kito F, et al. Establishment and characterizationof cell line of undifferentiated pleomorphic sarcoma. Tiss Cult Res Commun. 2017;36:41–8.

    Google Scholar 

  38. Iyer SP, Foss FF. Romidepsin for the treatment of peripheral T-cell lymphoma. Oncologist. 2015;20:1084–91.

    Article  CAS  Google Scholar 

  39. Becker M, Graf C, Tonak M, et al. Xenograft models for undifferentiated pleomorphic sarcoma not otherwise specified are essential for preclinical testing of therapeutic agents. Oncol Lett. 2016;12:1257–64.

    Article  CAS  Google Scholar 

  40. Saitoh Y, Bureta C, Sasaki H, et al. The histone deacetylase inhibitor LBH589 inhibits undifferentiated pleomorphic sarcoma growth via downregulation of FOS-like antigen 1. Mol Carcinog. 2019;58:234–46.

    Article  CAS  Google Scholar 

  41. Rivera-Reyes A, Ye S, Gloria EM, et al. YAP1 enhances NF-kappaB-dependent and independent effects on clock-mediated unfolded protein responses and autophagy in sarcoma. Cell Death Dis. 2018;9:1108.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Drs. E. Kobayashi, S. Iwata, S. Fukushima, M. Nakagawa, S. Ozaki, C. Sato (Department of Musculoskeletal Oncology), Dr. T. Ushikusa (Department of Diagnostic Pathology), and the 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 like to thank Editage (www.editage.jp) for their help with English language editing and constructive comments on the manuscript. This research was received technical assistance from the Fundamental Innovative Oncology Core at the National Cancer Center.

Funding

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

Author information

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, Taro Akiyama & 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, Taro Akiyama & Seiji Ohtori

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

    Jun Sugaya, Fumihiko Nakatani & Akira Kawai

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

    Naoki Kojima & Akihiko Yoshida

Authors
  1. Ryuto Tsuchiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuki Yoshimatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rei Noguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yooksil Sin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takuya Ono
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Taro Akiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jun Sugaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fumihiko Nakatani
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Naoki Kojima
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Akihiko Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Seiji Ohtori
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Akira Kawai
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Tadashi Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tadashi Kondo.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

The ethical committee of the National Cancer Center approved the use of clinical materials for this study (approval number 2004-050).

Informed consent

Written informed consent for publication was provided by the patient.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (XLSX 14 KB)

Supplementary file2 (XLSX 25 KB)

Supplementary file3 (XLSX 39 KB)

Supplementary file4 (XLSX 25 KB)

Supplementary file5 (XLSX 11 KB)

Supplementary file6 Supplementary Fig. 1 Immunohistochemical findings (TIF 2310 KB)

Supplementary file7 Supplementary Fig. 2 Short tandem repeat analysis (TIF 217 KB)

13577_2021_633_MOESM8_ESM.tif

Supplementary file8 Supplementary Fig. 3 Tumorigenesis in nude mice. (A) NCC-UPS3-C1 cells transplanted into BALB/c nude mice formed a small tumor mass under the described condition. The yellow circles indicate the tumor. (B) The H&E-stained tumor represents the dense proliferation of pleomorphic cells. (C) The graph showing estimated tumor volume. Bars represent the mean standard error (TIF 1337 KB)

13577_2021_633_MOESM9_ESM.tif

Supplementary file9 Supplementary Fig. 4 Growth curves for the IC50 value calculations of 24 anticancer agents (TIF 618 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tsuchiya, R., Yoshimatsu, Y., Noguchi, R. et al. Establishment and characterization of NCC-UPS3-C1: a novel patient-derived cell line of undifferentiated pleomorphic sarcoma. Human Cell 35, 384–391 (2022). https://doi.org/10.1007/s13577-021-00633-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-021-00633-w

Keywords

Search

Navigation