Generation of novel patient-derived CIC- DUX4 sarcoma xenografts and cell lines

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...

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Autores principales:	Rieko Oyama, Mami Takahashi, Akihiko Yoshida, Marimu Sakumoto, Yoko Takai, Fusako Kito, Kumiko Shiozawa, Zhiwei Qiao, Yasuhito Arai, Tatsuhiro Shibata, Yoshihiro Araki, Makoto Endo, Akira Kawai, Tadashi Kondo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/038c203a9ecf41ae9dccc27b7bd992e6
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spelling	oai:doaj.org-article:038c203a9ecf41ae9dccc27b7bd992e62021-12-02T15:18:52ZGeneration of novel patient-derived CIC- DUX4 sarcoma xenografts and cell lines10.1038/s41598-017-04967-02045-2322https://doaj.org/article/038c203a9ecf41ae9dccc27b7bd992e62017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04967-0https://doaj.org/toc/2045-2322Abstract 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.Rieko OyamaMami TakahashiAkihiko YoshidaMarimu SakumotoYoko TakaiFusako KitoKumiko ShiozawaZhiwei QiaoYasuhito AraiTatsuhiro ShibataYoshihiro ArakiMakoto EndoAkira KawaiTadashi KondoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rieko Oyama Mami Takahashi Akihiko Yoshida Marimu Sakumoto Yoko Takai Fusako Kito Kumiko Shiozawa Zhiwei Qiao Yasuhito Arai Tatsuhiro Shibata Yoshihiro Araki Makoto Endo Akira Kawai Tadashi Kondo Generation of novel patient-derived CIC- DUX4 sarcoma xenografts and cell lines
description	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.
format	article
author	Rieko Oyama Mami Takahashi Akihiko Yoshida Marimu Sakumoto Yoko Takai Fusako Kito Kumiko Shiozawa Zhiwei Qiao Yasuhito Arai Tatsuhiro Shibata Yoshihiro Araki Makoto Endo Akira Kawai Tadashi Kondo
author_facet	Rieko Oyama Mami Takahashi Akihiko Yoshida Marimu Sakumoto Yoko Takai Fusako Kito Kumiko Shiozawa Zhiwei Qiao Yasuhito Arai Tatsuhiro Shibata Yoshihiro Araki Makoto Endo Akira Kawai Tadashi Kondo
author_sort	Rieko Oyama
title	Generation of novel patient-derived CIC- DUX4 sarcoma xenografts and cell lines
title_short	Generation of novel patient-derived CIC- DUX4 sarcoma xenografts and cell lines
title_full	Generation of novel patient-derived CIC- DUX4 sarcoma xenografts and cell lines
title_fullStr	Generation of novel patient-derived CIC- DUX4 sarcoma xenografts and cell lines
title_full_unstemmed	Generation of novel patient-derived CIC- DUX4 sarcoma xenografts and cell lines
title_sort	generation of novel patient-derived cic- dux4 sarcoma xenografts and cell lines
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/038c203a9ecf41ae9dccc27b7bd992e6
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Generation of novel patient-derived CIC- DUX4 sarcoma xenografts and cell lines

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