| Synovial sarcoma is a stem cell malignancy. | |
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MedLine Citation:
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PMID: 20518020 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Synovial sarcoma (SS) is a malignant soft tissue tumor characterized by its unique t(X;18)(p11;q11) chromosomal translocation leading to the formation of the SS18-SSX fusion gene. The resulting fusion protein product is considered to play as an aberrant transcription factor and transform target cells by perturbing their gene expression program. However, the cellular origin of SS is highly debated. We herein established two novel human SS cell lines, named Yamato-SS and Aska-SS, and investigated their biological properties. We found the self-renewal ability of these cells to generate sarcospheres, to form tumors in serial xenotransplantation and reconstitute the tumor phenotypes without fractionation by any surface markers. Both SS cells as well as clinical tissue specimens from 15 patients expressed the marker genes-associated stem cell identity, Oct3/4, Nanog, and Sox2. We also found that both SS cells displayed limited differentiation potentials for mesenchymal lineages into osteocytes and chondrocytes albeit with the expression of early mesenchymal and hematopoietic lineage genes. Upon SS18-SSX silencing with sequence-specific siRNAs, these SS cells exhibited morphological transition from spherical growth in suspension to adherent growth in monolayer, additional expression of later mesenchymal and hematopoietic lineage genes, and broader differentiation potentials into osteocytes, chondrocytes, adipocytes, and macrophages in appropriate differentiation cocktails. Collectively, these data suggest that a human multipotent mesenchymal stem cell can serve as a cell of origin for SS and SS is a stem cell malignancy resulting from dysregulation of self-renewal and differentiation capacities driven by SS18-SSX fusion protein. |
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Authors:
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Norifumi Naka; Satoshi Takenaka; Nobuhito Araki; Toshitada Miwa; Nobuyuki Hashimoto; Kiyoko Yoshioka; Susumu Joyama; Ken-Ichiro Hamada; Yoshitane Tsukamoto; Yasuhiko Tomita; Takafumi Ueda; Hideki Yoshikawa; Kazuyuki Itoh |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Stem cells (Dayton, Ohio) Volume: 28 ISSN: 1549-4918 ISO Abbreviation: Stem Cells Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-27 Completed Date: 2010-11-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9304532 Medline TA: Stem Cells Country: United States |
Other Details:
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Languages: eng Pagination: 1119-31 Citation Subset: IM |
Affiliation:
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Musculoskeletal Oncology Service, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka, Japan. naka-no@mc.pref.osaka.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Culture Techniques Cell Differentiation Cell Lineage Gene Expression Regulation, Neoplastic Humans Mice Mice, Nude Neoplastic Stem Cells / cytology, metabolism* Oncogene Proteins, Fusion / genetics, metabolism RNA, Small Interfering / genetics Sarcoma, Synovial / genetics, metabolism*, pathology Tumor Cells, Cultured Xenograft Model Antitumor Assays |
| Chemical | |
Reg. No./Substance:
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0/Oncogene Proteins, Fusion; 0/RNA, Small Interfering; 0/SYT-SSX fusion protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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