CIC-DUX4 sarcoma (CDS) is a group of rare, mesenchymal, small round cell tumours that harbour the unique CIC-DUX4 translocation, which causes aberrant gene expression. CDS exhibits an aggressive course and poor clinical outcome, thus novel therapeutic approaches are needed for CDS treatment. Although patient-derived cancer models are an essential modality to develop novel therapies, none currently exist for CDS. Thus, the present study successfully established CDS patient-derived xenografts and subsequently generated two CDS cell lines from the grafted tumours. Notably, xenografts were histologically similar to the original patient tumour, and the expression of typical biomarkers was confirmed in the xenografts and cell lines. Moreover, the xenograft tumours and cell lines displayed high Src kinase activities, as assessed by peptide-based tyrosine kinase array. Upon screening 119 FDA-approved anti-cancer drugs, we found that only actinomycine D and doxorubicin were effectively suppress the proliferation among the drugs for standard therapy for Ewing sarcoma. However, we identified molecular targeting reagents, such as bortezomib and crizotinib that markedly suppressed the growth of CDS cells. Our models will be useful modalities to develop novel therapeutic strategies against CDS.
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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