The CAM Model for CIC-DUX4 Sarcoma and Its Potential Use for Precision Medicine

• Published in: Cells (Basel, Switzerland) Switzerland), 2021-10, Vol.10 (10), p.2613
• Main Authors: Komatsu, Aoi, Matsumoto, Kotaro, Yoshimatsu, Yuki, Sin, Yooksil, Kubota, Arisa, Saito, Tomoki, Mizumoto, Ayaka, Ohashi, Shinya, Muto, Manabu, Noguchi, Rei, Kondo, Tadashi, Tamanoi, Fuyuhiko
• Format: Article
• Language: English
• Subjects: Animal models; Biomarkers, Tumor - metabolism; CAM assay; Cancer; Cell cycle; Cell Line, Tumor; Chorioallantoic membrane; Chorioallantoic Membrane - metabolism; Chorioallantoic Membrane - pathology; CIC-DUX4 sarcoma; Cyclin D2; DNA polymerase; Eggs; Ewings sarcoma; fusion gene; Fusion protein; Gene expression; H&E staining; Homeodomain Proteins - metabolism; Humans; Humidity; Immunohistochemistry; Mesenchyme; Oncogene Proteins, Fusion - metabolism; Organoids; Polymerase chain reaction; Precision medicine; rare cancer; Repressor Proteins - metabolism; Sarcoma; Sarcoma - metabolism; Transcription factors; Tumor cell lines; Tumors; Western blotting
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells10102613

(1) Background: sarcoma is a rare mesenchymal small round cell tumor which belongs to rare cancers that occupy a significant percentage of cancer cases as a whole, despite each being rare. Importantly, each rare cancer type has different features, and thus there is a need to develop a model that mimics the features of each of these cancers. We evaluated the idea that the chicken chorioallantoic membrane assay (CAM), a convenient and versatile animal model, can be established for the sarcoma. (2) Methods: Patient-derived cell lines of were applied. These cells were transplanted onto the CAM membrane and tumor formation was examined by H&E staining, immunohistochemistry and Western blotting. The CAM tumor was transferred onto a fresh CAM and was also used to form organoids. Retention of the fusion gene was examined. (3) Results: H&E staining as well as molecular characterization demonstrated the formation of the tumor on the CAM membrane. Expression of cyclin D2 and ETV4 was identified. The CAM tumor was transferred to a fresh CAM to form the second-generation CAM tumor. In addition, we were successful in forming tumor organoids using the CAM tumor. Retention of the fusion gene in the CAM, second-generation CAM, and in the CAM-derived organoids was confirmed by RT-PCR. (4) Conclusions: The CAM assay provides a promising model for sarcoma.