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Establishment and characterization of NCC-ASPS2-C1: a novel patient-derived cell line of alveolar soft part sarcoma

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Abstract

Alveolar soft part sarcoma (ASPS) is a rare mesenchymal tumor characterized by rearrangement of the ASPSCR1 and TFE3 genes and a histologically distinctive pseudoalveolar pattern. ASPS progresses slowly, but is prone to late metastasis. As ASPS is refractory to conventional chemotherapy, the only curative treatment is complete surgical resection. The prognosis of advanced and metastatic cases is poor, highlighting the need for preclinical research to develop appropriate treatment options. However, ASPS is extremely rare, accounting for < 1% of all soft tissue sarcomas, and only one patient-derived ASPS cell line is available from public cell banks worldwide for research. This study reports the establishment of a novel ASPS cell line derived from the primary tumor tissue of an ASPS patient, named NCC-ASPS2-C1. This cell line retains the ASPSCR1–TFE3 fusion gene, which is characteristic of ASPS. The characterization of this cell line revealed stable growth, spheroid formation, and invasive properties. By screening a drug library using NCC-ASPS2-C1, we identified several drugs that inhibited the proliferation of ASPS cells. In conclusion, the establishment of NCC-ASPS2-C1 provides a valuable resource for advancing ASPS research and developing novel treatments for this challenging disease.

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References

  1. board WHOcte. Soft tissue and bone tumours. 5th ed ed. World Health Organization classification of tumours. World Health Organization International Agency for Research on Cancer; 2020.

  2. Ladanyi M, Lui MY, Antonescu CR, Krause-Boehm A, Meindl A, Argani P, et al. The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. Oncogene. 2001;20(1):48–57. https://doi.org/10.1038/sj.onc.1204074.

    Article  CAS  PubMed  Google Scholar 

  3. S Joyama, T Ueda, K Shimizu, I Kudawara, M Mano, H Funai et al. 1999 Chromosome rearrangement at 17q25 and xp11.2 in alveolar soft-part sarcoma: A case report and review of the literature. Cancer 86(7) 1246–1250.

  4. Fujiwara T, Kunisada T, Nakata E, Nishida K, Yanai H, Nakamura T, et al. Advances in treatment of alveolar soft part sarcoma: an updated review. Jpn J Clin Oncol. 2023;53(11):1009–18. https://doi.org/10.1093/jjco/hyad102.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Li W, Zhang S, Fan W, Li D, Tian H, Che D, et al. Sonographic imaging features of alveolar soft part sarcoma: Case series and literature review. Medicine. 2022;101(46): e31905. https://doi.org/10.1097/md.0000000000031905.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Hashimoto H. Incidence of soft tissue sarcomas in adults. Curr Top Pathol. 1995;89:1–16. https://doi.org/10.1007/978-3-642-77289-4_1.

    Article  CAS  PubMed  Google Scholar 

  7. Wang H, Jacobson A, Harmon DC, Choy E, Hornicek FJ, Raskin KA, et al. Prognostic factors in alveolar soft part sarcoma: A SEER analysis. J Surg Oncol. 2016;113(5):581–6. https://doi.org/10.1002/jso.24183.

    Article  PubMed  Google Scholar 

  8. PH Lieberman, MF Brennan, M Kimmel, RA Erlandson, P Garin-Chesa, BY Flehinger. 1989 Alveolar soft-part sarcoma. A clinico-pathologic study of half a century. Cancer 63(1) 1–13. doi:https://doi.org/10.1002/1097-0142(19890101)63:1<1::aid-cncr2820630102>3.0.co;2-e.

  9. de Barros GF, Hakim JR, Passos JP, Perron M, Odashiro AN. Orbital alveolar soft part sarcoma: case report and literature review. Can J Ophthalmol. 2019;54(6):e292–4. https://doi.org/10.1016/j.jcjo.2019.02.005.

    Article  PubMed  Google Scholar 

  10. Eley KA, Afzal T, Shah KA, Watt-Smith SR. Alveolar soft-part sarcoma of the tongue: report of a case and review of the literature. Int J Oral Maxillofac Surg. 2010;39(8):824–6. https://doi.org/10.1016/j.ijom.2010.02.020.

    Article  CAS  PubMed  Google Scholar 

  11. Portera CA Jr, Ho V, Patel SR, Hunt KK, Feig BW, Respondek PM, et al. Alveolar soft part sarcoma: clinical course and patterns of metastasis in 70 patients treated at a single institution. Cancer. 2001;91(3):585–91. https://doi.org/10.1002/1097-0142(20010201)91:3%3c585::aid-cncr1038%3e3.0.co;2-0.

    Article  PubMed  Google Scholar 

  12. Kayton ML, Meyers P, Wexler LH, Gerald WL, LaQuaglia MP. Clinical presentation, treatment, and outcome of alveolar soft part sarcoma in children, adolescents, and young adults. J Pediatr Surg. 2006;41(1):187–93. https://doi.org/10.1016/j.jpedsurg.2005.10.023.

    Article  PubMed  Google Scholar 

  13. Fujiwara T, Nakata E, Kunisada T, Ozaki T, Kawai A. Alveolar soft part sarcoma: progress toward improvement in survival? A population-based study. BMC Cancer. 2022;22(1):891. https://doi.org/10.1186/s12885-022-09968-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lazar AJ, Das P, Tuvin D, Korchin B, Zhu Q, Jin Z, et al. Angiogenesis-promoting gene patterns in alveolar soft part sarcoma. Clin Cancer Res. 2007;13(24):7314–21. https://doi.org/10.1158/1078-0432.Ccr-07-0174.

    Article  CAS  PubMed  Google Scholar 

  15. Penel N, Coindre JM, Giraud A, Terrier P, Ranchere-Vince D, Collin F, et al. Presentation and outcome of frequent and rare sarcoma histologic subtypes: A study of 10,262 patients with localized visceral/soft tissue sarcoma managed in reference centers. Cancer. 2018;124(6):1179–87. https://doi.org/10.1002/cncr.31176.

    Article  PubMed  Google Scholar 

  16. Soheilifar MH, Taheri RA, Zolfaghari Emameh R, Moshtaghian A, Kooshki H, Motie MR. Molecular landscape in alveolar soft part sarcoma: implications for molecular targeted therapy. Biomed Pharmacother. 2018;103:889–96. https://doi.org/10.1016/j.biopha.2018.04.117.

    Article  CAS  PubMed  Google Scholar 

  17. Kim M, Kim TM, Keam B, Kim YJ, Paeng JC, Moon KC, et al. A phase II trial of pazopanib in patients with metastatic alveolar soft part sarcoma. Oncologist. 2019;24(1):20-e9. https://doi.org/10.1634/theoncologist.2018-0464.

    Article  CAS  PubMed  Google Scholar 

  18. Judson I, Morden JP, Kilburn L, Leahy M, Benson C, Bhadri V, et al. Cediranib in patients with alveolar soft-part sarcoma (CASPS): a double-blind, placebo-controlled, randomised, phase 2 trial. Lancet Oncol. 2019;20(7):1023–34. https://doi.org/10.1016/s1470-2045(19)30215-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Schöffski P, Wozniak A, Kasper B, Aamdal S, Leahy MG, Rutkowski P, et al. Activity and safety of crizotinib in patients with alveolar soft part sarcoma with rearrangement of TFE3: European Organization for Research and Treatment of Cancer (EORTC) phase II trial 90101 “CREATE.” Ann Oncol. 2018;29(3):758–6578. https://doi.org/10.1093/annonc/mdx774.

    Article  PubMed  Google Scholar 

  20. Jagodzińska-Mucha P, Świtaj T, Kozak K, Koseła-Paterczyk H, Klimczak A, Ługowska I, et al. Long-term results of therapy with sunitinib in metastatic alveolar soft part sarcoma. Tumori. 2017;103(3):231–5. https://doi.org/10.5301/tj.5000617.

    Article  CAS  PubMed  Google Scholar 

  21. Kondo T. Current status and future outlook for patient-derived cancer models from a rare cancer research perspective. Cancer Sci. 2021;112(3):953–61. https://doi.org/10.1111/cas.14669.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ono T, Noguchi R, Yoshimatsu Y, Sin Y, Tsuchiya R, Akiyama T, et al. Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone. Hum Cell. 2023;36(5):1804–12. https://doi.org/10.1007/s13577-023-00928-0.

    Article  CAS  PubMed  Google Scholar 

  23. Billiau A, Edy VG, Heremans H, Van Damme J, Desmyter J, Georgiades JA, et al. Human interferon: mass production in a newly established cell line, MG-63. Antimicrob Agents Chemother. 1977;12(1):11–5. https://doi.org/10.1128/aac.12.1.11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Dickson BC, Chung CT, Hurlbut DJ, Marrano P, Shago M, Sung YS, et al. Genetic diversity in alveolar soft part sarcoma: A subset contain variant fusion genes, highlighting broader molecular kinship with other MiT family tumors. Genes Chromosomes Cancer. 2020;59(1):23–9. https://doi.org/10.1002/gcc.22803.

    Article  CAS  PubMed  Google Scholar 

  25. Langhans SA. Three-dimensional in vitro cell culture models in drug discovery and drug repositioning. Front Pharmacol. 2018;9:6. https://doi.org/10.3389/fphar.2018.00006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jensen C, Teng Y. Is it time to start transitioning from 2D to 3D cell culture? Front Mol Biosci. 2020;7:33. https://doi.org/10.3389/fmolb.2020.00033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. O’Sullivan Coyne G, Naqash AR, Sankaran H, Chen AP. Advances in the management of alveolar soft part sarcoma. Curr Probl Cancer. 2021;45(4): 100775. https://doi.org/10.1016/j.currproblcancer.2021.100775.

    Article  PubMed  Google Scholar 

  28. Paoluzzi L, Maki RG. Diagnosis, prognosis, and treatment of alveolar soft-part sarcoma: a review. JAMA Oncol. 2019;5(2):254–60. https://doi.org/10.1001/jamaoncol.2018.4490.

    Article  PubMed  Google Scholar 

  29. Schuetze SM, Bolejack V, Choy E, Ganjoo KN, Staddon AP, Chow WA, et al. Phase 2 study of dasatinib in patients with alveolar soft part sarcoma, chondrosarcoma, chordoma, epithelioid sarcoma, or solitary fibrous tumor. Cancer. 2017;123(1):90–7. https://doi.org/10.1002/cncr.30379.

    Article  CAS  PubMed  Google Scholar 

  30. Wadman M. FDA no longer has to require animal testing for new drugs. Science. 2023;379(6628):127–8. https://doi.org/10.1126/science.adg6276.

    Article  CAS  PubMed  Google Scholar 

  31. Nuwer R. US agency seeks to phase out animal testing. Nature. 2022. https://doi.org/10.1038/d41586-022-03569-9.

    Article  PubMed  Google Scholar 

  32. Cauli E, Polidoro MA, Marzorati S, Bernardi C, Rasponi M, Lleo A. Cancer-on-chip: a 3D model for the study of the tumor microenvironment. J Biol Eng. 2023;17(1):53. https://doi.org/10.1186/s13036-023-00372-6.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Drs. S. Iwata, K. Ogura, and S. Fukushima (Department of Musculoskeletal Oncology and Rehabilitation Medicine, National Cancer Center Hospital); Dr. T. Funada, and Dr. Y. Kobayashi (Department of Diagnostic Pathology, National Cancer Center Hospital); and National Cancer Center Hospital for sampling the tumor tissue specimens from the surgically resected materials. We appreciate the technical support provided by Mrs. Y. Shiotani (Central Animal Division, National Cancer Center Research Institute). We appreciate the technical assistance provided by Mr. Y. Ono (Division of Rare Cancer Research, National Cancer Center Research Institute). We would also like to thank Editage (www.editage.jp) for their help with the English language editing and constructive comments on the manuscript. This study was supported by the Fundamental Innovative Oncology Core of the National Cancer Center (Tokyo, Japan).

Funding

This research was supported by the Japan Agency for Medical Research and Development (Grant number: 20ck0106537h).

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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

    Julia Osaki, Rei Noguchi, Kazuyoshi Yanagihara, Takuya Ono, Yuki Adachi, Shuhei Iwata & Tadashi Kondo

  2. Department of Musculoskeletal Oncology and Rehabilitation Medicine, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan

    Yu Toda, Tetsuya Sekita, Eisuke Kobayashi & Akira Kawai

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

    Naoki Kojima & Akihiko Yoshida

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  1. Julia Osaki
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Correspondence to Tadashi Kondo.

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Osaki, J., Noguchi, R., Yanagihara, K. et al. Establishment and characterization of NCC-ASPS2-C1: a novel patient-derived cell line of alveolar soft part sarcoma. Human Cell 37, 865–873 (2024). https://doi.org/10.1007/s13577-024-01039-0

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