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Generation of novel patient-derived CIC-DUX4 sarcoma xenografts and cell lines
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. Althoug...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498486/ https://www.ncbi.nlm.nih.gov/pubmed/28680140 http://dx.doi.org/10.1038/s41598-017-04967-0 |
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author | 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 |
author_facet | 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 |
author_sort | Oyama, Rieko |
collection | PubMed |
description | 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 | Online Article Text |
id | pubmed-5498486 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-54984862017-07-10 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 Sci Rep Article 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. Nature Publishing Group UK 2017-07-05 /pmc/articles/PMC5498486/ /pubmed/28680140 http://dx.doi.org/10.1038/s41598-017-04967-0 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article 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 Generation of novel patient-derived CIC-DUX4 sarcoma xenografts and cell lines |
title | 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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498486/ https://www.ncbi.nlm.nih.gov/pubmed/28680140 http://dx.doi.org/10.1038/s41598-017-04967-0 |
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