1. Detection of Metastasis in a Patient-derived Orthotopic Xenograft (PDOX) Model of Undifferentiated Pleomorphic Sarcoma with Red Fluorescent Protein
- Author
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Robert M. Hoffman, Michael Bouvet, Tasuku Kiyuna, Hiromichi Oshiro, Scott D. Nelson, Takashi Higuchi, Yunfeng Li, Kentaro Miyake, Yasunori Tome, Sahar Razmjooei, Sintawat Wangsiricharoen, Maryam Barangi, Fuminori Kanaya, Masuyo Miyake, Zhiying Zhang, Shree Ram Singh, and Kei Kawaguchi
- Subjects
Cancer Research ,Stromal cell ,Histiocytoma, Malignant Fibrous ,Undifferentiated Pleomorphic Sarcoma ,law.invention ,Metastasis ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Confocal microscopy ,law ,medicine ,Animals ,Humans ,Neoplasm Metastasis ,business.industry ,Soft tissue sarcoma ,Cancer ,Cell Differentiation ,Sarcoma ,General Medicine ,medicine.disease ,Primary tumor ,Xenograft Model Antitumor Assays ,Luminescent Proteins ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,business - Abstract
Background/aim Undifferentiated pleomorphic sarcoma (UPS) is a common soft tissue sarcoma and highly recalcitrant. We have previously developed patient-derived orthotopic xenograft (PDOX) mouse models of UPS and other major sarcoma types. Unlike PDOX models of other cancer types, it has been difficult to demonstrate metastasis in the sarcoma PDOX models. Materials and methods To visualize metastasis at high resolution in the UPS PDOX model, established tumor fragments were implanted in transgenic nude mice expressing red fluorescent protein (RFP) for one passage. The tumors acquired RFP-expressing stroma from transgenic host. UPS tumor with RFP stromal cells were harvested and implanted orthotopically in non-transgenic nude mice. After six weeks of UPS tumor growth in the PDOX model, the primary tumor was imaged non-invasively and lung, liver, and spleen were resected and imaged ex-vivo in order to visualize the presence of RFP, with a FluorVivo® imaging system and FV1000® confocal laser microscope, respectively. Results The primary tumor was imaged non-invasively. Confocal microscopy visualized the presence of RFP in the lung and liver indicating metastases in these organs. This is the first report of metastasis in a sarcoma PDOX model. Conclusion This study should prove very useful to screen for anti-metastatic drugs for the PDOX donor patients and to understand the metastatic process in sarcoma.
- Published
- 2019