Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 4712 |
| Journal | Scientific Reports |
| Volume | 7 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 5 2017 |
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Generation of novel patient-derived CIC- DUX4 sarcoma xenografts and cell lines. / Oyama, Rieko; Takahashi, Mami; Yoshida, Akihiko; Sakumoto, Marimu; Takai, Yoko; Kito, Fusako; Shiozawa, Kumiko; Qiao, Zhiwei; Arai, Yasuhito; Shibata, Tatsuhiro; Araki, Yoshihiro; Endo, Makoto; Kawai, Akira; Kondo, Tadashi.
In: Scientific Reports, Vol. 7, No. 1, 05.07.2017, p. 4712.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Generation of novel patient-derived CIC- DUX4 sarcoma xenografts and cell lines
AU - Oyama, Rieko
AU - Takahashi, Mami
AU - Yoshida, Akihiko
AU - Sakumoto, Marimu
AU - Takai, Yoko
AU - Kito, Fusako
AU - Shiozawa, Kumiko
AU - Qiao, Zhiwei
AU - Arai, Yasuhito
AU - Shibata, Tatsuhiro
AU - Araki, Yoshihiro
AU - Endo, Makoto
AU - Kawai, Akira
AU - Kondo, Tadashi
PY - 2017/7/5
Y1 - 2017/7/5
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-017-04967-0
DO - 10.1038/s41598-017-04967-0
M3 - Article
C2 - 28680140
VL - 7
SP - 4712
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
ER -