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Establishment and characterization of novel patient-derived osteosarcoma xenograft and cell line

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Abstract

Osteosarcoma is an aggressive mesenchymal malignancy of the bone. Patient-derived models are essential tools for elucidating the molecular mechanisms associated with poor prognosis and the development of novel anticancer drugs. This study described the establishment of a patient-derived cancer model of osteosarcoma. Primary osteosarcoma tumor tissues were obtained from an osteosarcoma patient and inoculated in the skin of immunodeficient mice, followed by transplantation to other mice upon growth. Cells were maintained in monolayer cultures, and the capability of spheroid formation was assessed by seeding the cells on culture dishes. The invasion ability of cells was monitored by Matrigel assay, and genomic and proteomic backgrounds were examined by mass spectrometry. A cell line was established from patient-derived tumors and showed similar histology to that of the primary tumor tissue. Additionally, these cells formed spheroids on low-attachment tissue-culture dishes and exhibited invasive capabilities, and we confirmed that the genomic backgrounds were similar between patient-derived xenograft tumors and the cell line. Furthermore, the proteome of the patient-derived tumors and the cells exhibited similar, but not identical, patterns to that of the original tumor tissue. Our results indicated that this patient-derived xenograft model and cell line would be useful resources for osteosarcoma research.

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Acknowledgments

We appreciate Drs. M. Endo, Y. Minami, K. Shimizu, T. Mori, T. Uehara M. Sugawara, Y. Araki, S. Toki, and Ms. R. Nakano, Division of Musculoskeletal Oncology, National Cancer Center Hospital, for sampling tumor-tissue specimens from surgically resected materials. We would also like to thank Editage (www.editage.jp) for English-language editing and their constructive comments on the manuscript. This research was supported by the National Cancer Center Research and Development Fund (grant nos. 26-A-3, 26-A-9, and 29-A-2), and by the Fundamental Innovative Oncology Core in the National Cancer Center.

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Authors and Affiliations

  1. Department of Innovative Seeds Evaluation, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Fusako Kito, Rieko Oyama, Marimu Sakumoto & Tadashi Kondo

  2. Central Animal Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Mami Takahashi

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

    Kumiko Shiozawa, Zhiwei Qiao & Tadashi Kondo

  4. Department of Clinical Genomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Hiromi Sakamoto

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

    Takeshi Hirose, Nokitaka Setsu & Akira Kawai

  6. Pathology and Clinical Laboratory Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Akihiko Yoshida

Authors
  1. Fusako Kito
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  2. Rieko Oyama
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  4. Mami Takahashi
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  6. Zhiwei Qiao
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  7. Hiromi Sakamoto
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  8. Takeshi Hirose
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  9. Nokitaka Setsu
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  10. Akihiko Yoshida
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  11. Akira Kawai
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  12. Tadashi Kondo
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Corresponding author

Correspondence to Tadashi Kondo.

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This study was approved by the Ethics Committee of the National Cancer Center, and both informed assent and informed consent were obtained from the patient and his parents.

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Editor: Tetsuji Okamoto

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Kito, F., Oyama, R., Sakumoto, M. et al. Establishment and characterization of novel patient-derived osteosarcoma xenograft and cell line. In Vitro Cell.Dev.Biol.-Animal 54, 528–536 (2018). https://doi.org/10.1007/s11626-018-0274-2

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  • DOI: https://doi.org/10.1007/s11626-018-0274-2

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