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Neuronal Differentiation of Synovial Sarcoma and Its Therapeutic Application

  • Symposium: Molecular Genetics in Sarcoma
  • Published:
Clinical Orthopaedics and Related Research

Abstract

Synovial sarcoma is a rare sarcoma of unknown histologic origin. We previously reported the gene expression profile of synovial sarcoma was closely related to that of malignant peripheral nerve sheath tumors, and the fibroblast growth factor (FGF) signal was one of the main growth signals in synovial sarcoma. Here we further demonstrate the neural origin of synovial sarcoma using primary tumors and cell lines. The expression of neural tissue-related genes was confirmed in synovial sarcoma tumor tissues, but the expression of some genes was absent in synovial sarcoma cell lines. Treatment of synovial sarcoma cell lines with BMP4 or FGF2 enhanced or restored the expression of neural tissue-related genes and induced a neuron-like morphology with positive Tuj-1 expression. Treatment with all-trans-retinoic acid also induced the expression of neural tissue-related genes in association with growth inhibition, which was not observed in other cell lines except a malignant peripheral nerve sheath tumor cell line. A growth-inhibitory effect of all-trans-retinoic acid was also observed for xenografted tumors in athymic mice. The simultaneous treatment with FGF signal inhibitors enhanced the growth-inhibitory effect of all-trans-retinoic acid, suggesting the combination of growth signaling inhibition and differentiation induction could be a potential molecular target for treating synovial sarcoma.

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Acknowledgments

We thank Drs Koichi Nishijo, Kotaro R. Shibata, Yasuko Shima, Yoshiki Kohno, Kenichi Fukiage, Seiji Otsuka, Moritoshi Furu, Kinya Ito, Yonghui Jin, and Yoichiro Kajita for their contribution to this study.

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Authors and Affiliations

  1. Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Tatsuya Ishibe MD, PhD, Tomoki Aoyama MD, PhD & Junya Toguchida MD, PhD

  2. Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Tatsuya Ishibe MD, PhD, Tomitaka Nakayama MD, PhD & Takashi Nakamura MD, PhD

Authors
  1. Tatsuya Ishibe MD, PhD
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  2. Tomitaka Nakayama MD, PhD
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  3. Tomoki Aoyama MD, PhD
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  4. Takashi Nakamura MD, PhD
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  5. Junya Toguchida MD, PhD
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Corresponding author

Correspondence to Junya Toguchida MD, PhD.

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Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

Each author certifies that his institution has approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained. Each author also certifies that his or her institution has approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

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Ishibe, T., Nakayama, T., Aoyama, T. et al. Neuronal Differentiation of Synovial Sarcoma and Its Therapeutic Application. Clin Orthop Relat Res 466, 2147–2155 (2008). https://doi.org/10.1007/s11999-008-0343-z

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  • DOI: https://doi.org/10.1007/s11999-008-0343-z

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