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Establishment of novel patient-derived models of dermatofibrosarcoma protuberans: two cell lines, NCC-DFSP1-C1 and NCC-DFSP2-C1

  • Rieko Oyama
  • Fusako Kito
  • Zhiwei Qiao
  • Marimu Sakumoto
  • Kumiko Shiozawa
  • Shunichi Toki
  • Akihiko Yoshida
  • Akira Kawai
  • Tadashi KondoEmail author
Article

Abstract

Dermatofibrosarcoma protuberans (DFSP) is a common type of dermal sarcoma, characterized by the presence of the unique collagen type I alpha 1 chain (COL1A1)-PDGFB translocation, which causes constitutive activation of the platelet-derived growth factor β (PDGFB) signaling pathway. Patients with DFSP exhibit frequent local recurrence, and novel therapeutic approaches are required to achieve better clinical outcomes. Patient-derived cancer cell lines are essential in the preclinical research. Here, we established novel patient-derived DFSP cell lines from two patients with DFSP and designated these cell lines NCC-DFSP1-C1 and NCC-DFSP2-C1. Tumors of the two patients with DFSP had COL1A1-PDGFB translocations with distinct COL1A1 breakpoints, e.g., in exons 33 and 15, and the translocations were preserved in the established cell lines. NCC-DFSP1-C1 and NCC-DFSP2-C1 cells exhibited similar morphology and limited capability of proliferation in vitro, forming spheroids when seeded on low-attachment tissue culture plates. In contrast, NCC-DFSP1-C1 cells had considerably higher invasive capability than NCC-DFSP2-C1 cells. Overall proteome contents were similar between NCC-DFSP1-C1 and NCC-DFSP2-C1 cells. Notably, in vitro screening studies identified anticancer drugs that showed antiproliferative effects at considerably low concentrations in the DFSP cell lines. Bortezomib, mitoxantrone, ponatinib, and romidepsin were more cytotoxic to NCC-DFSP1-C1 cells than to NCC-DFSP2-C1 cells. These cell lines will be useful tools for developing novel therapeutic strategies to treat DFSP.

Keywords

Dermatofibrosarcoma protuberans Patient-derived cell lines Anticancer drug COL1A1-PDGFB translocation 

Notes

Acknowledgments

We thank Drs. Y. Minami, K. Shimizu, T. Uehara, and M. Sugawara, T. Mori, as well as Ms. R. Nakano (Division of Musculoskeletal Oncology, National Cancer Center Hospital) for providing the tumor tissue specimens from surgically resected materials. This study was supported by the National Cancer Center Research and Development Fund (grant number 29-A-2). We would also like to thank Editage (www.editage.jp) for English language editing and constructive comments on the manuscript.

Compliance with ethical standards

Competing interests

The authors declare no competing financial interests.

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Copyright information

© The Society for In Vitro Biology 2018

Authors and Affiliations

  1. 1.Department of Innovative Seeds EvaluationNational Cancer Center Research InstituteTokyoJapan
  2. 2.Division of Rare Cancer ResearchNational Cancer Center Research InstituteTokyoJapan
  3. 3.Division of Musculoskeletal OncologyNational Cancer Center HospitalTokyoJapan
  4. 4.Department of Pathology and Clinical LaboratoriesNational Cancer Center HospitalTokyoJapan

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