ESTABLISHMENT AND CHARACTERIZATION OF PATIENT-DERIVED PLEOMORPHIC RHABDOMYOSARCOMA MODELS

DOI
  • OYAMA Rieko
    Department of Innovative Seeds Evaluation, National Cancer Center Research Institute
  • TAKAHASHI Mami
    Central Animal Division, National Cancer Center Research Institute
  • KITO Fusako
    Department of Innovative Seeds Evaluation, National Cancer Center Research Institute
  • SAKUMOTO Marimu
    Department of Innovative Seeds Evaluation, National Cancer Center Research Institute
  • TAKAI Yoko
    Department of Innovative Seeds Evaluation, National Cancer Center Research Institute
  • SHIOZAWA Kumiko
    Division of Rare Cancer Research, National Cancer Center Research Institute
  • QIAO Zhiwei
    Division of Rare Cancer Research, National Cancer Center Research Institute
  • TOKI Shunichi
    Division of Musculoskeletal Oncology, National Cancer Center Hospital
  • TANZAWA Yoshikazu
    Division of Musculoskeletal Oncology, National Cancer Center Hospital
  • YOSHIDA Akihiko
    Department of Pathology and Clinical Laboratories, National Cancer Center Hospital
  • KAWAI Akira
    Division of Musculoskeletal Oncology, National Cancer Center Hospital
  • KONDO Tadashi
    Department of Innovative Seeds Evaluation, National Cancer Center Research Institute Division of Rare Cancer Research, National Cancer Center Research Institute

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<p>Background: Pleomorphic rhabdomyosarcoma (pRMS) is an aggressive mesenchymal malignancy affecting adults, and its characteristics and clinical behaviors differ considerably from those of embryonal and alveolar RMS subtypes. A therapeutic strategy for pRMS has not been established, and its prognosis remains poor. Further investigations are therefore required to improve the clinical outcomes associated with this disease. Patient-derived cancer models are essential tools for basic and translational research, and numerous models of different RMS subtypes have been established. However, only two pRMS cell lines are available, and no xenograft model of this disease has been developed. Hence, the objective of this study was to establish patient-derived pRMS models.</p><p>Methods: We obtained tumor tissues from a 73-year-old pRMS patient who had not received chemotherapy or radiotherapy. We prepared patient-derived xenografts (PDXs) from these tumor tissues and stable patient-derived cell lines from both the original tumor and a PDX. The established models were then characterized, and their novelty was confirmed by short tandem repeat analysis.</p><p>Results: The PDX tumors were histologically similar to the original source tumor. Moreover, the established cell lines exhibited morphological features resembling those of RMS, the ability to form spheroids, constant growth, and invasive behavior. By screening an anti-cancer drug library, we identified mitoxantrone, ponatinib, romidepsin, vandetanib, belinostat, bortezomib, and vorinostat as potential drugs for pRMS treatment.</p><p>Conclusions: Our novel pRMS models will be useful research resources, providing an opportunity for in-depth investigations of the molecular basis and treatment of this disease. Clinical trials for the drugs showing anti-proliferative effects on pRMS cells may be worth considering in further studies.</p>

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