Cancer Stem Cells

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Synovial Sarcoma Is a Stem Cell Malignancy†‡§

  1. Norifumi Naka1,2,¶,*,
  2. Satoshi Takenaka2,3,
  3. Nobuhito Araki1,
  4. Toshitada Miwa4,
  5. Nobuyuki Hashimoto3,
  6. Kiyoko Yoshioka2,
  7. Susumu Joyama1,
  8. Ken-ichiro Hamada1,
  9. Yoshitane Tsukamoto5,
  10. Yasuhiko Tomita6,
  11. Takafumi Ueda7,
  12. Hideki Yoshikawa3,
  13. Kazuyuki Itoh2,‖,*

Article first published online: 1 JUN 2010

DOI: 10.1002/stem.452

Issue

STEM CELLS

STEM CELLS

Volume 28, Issue 7, pages 1119–1131, July 2010

Additional Information

How to Cite

Naka, N., Takenaka, S., Araki, N., Miwa, T., Hashimoto, N., Yoshioka, K., Joyama, S., Hamada, K.-i., Tsukamoto, Y., Tomita, Y., Ueda, T., Yoshikawa, H. and Itoh, K. (2010), Synovial Sarcoma Is a Stem Cell Malignancy. STEM CELLS, 28: 1119–1131. doi: 10.1002/stem.452

Author Information

  1. 1

    Musculoskeletal Oncology Service, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

  2. 2

    Departments of Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

  3. 3

    Department of Orthopedics, Osaka University Graduate School of Medicine, Osaka, Japan

  4. 4

    Department of Orthopedic Surgery, Osaka Koseinenkin Hospital, Osaka, Japan

  5. 5

    Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Japan

  6. 6

    Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

  7. 7

    Department of Orthopedic Surgery, Osaka National Hospital, Kinki-Block Comprehensive Cancer Center, Osaka, Japan

  1. Telephone: 81-6-6972-1181; Fax: 81-6-6973-5691

  2. ‖

    Telephone: 81-6-6972-1181; Fax: 81-6-6973-5691

*Musculoskeletal Oncology Service, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan

  1. †

    Author contributions: N.N.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; S.T., N.A., T.M., N.H., K.Y., S.J., K.H., Y.T., Y.T.: collection and assembly of data; T.U., H.Y.: provision of study material; K.I.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript.

  2. ‡

    First published online in STEM CELLS EXPRESS June 1, 2010; available online without subscription through the open access option.

  3. §

    Disclosure of potential conflicts of interest is found at the end of this article.

Publication History

  1. Issue published online: 20 JUL 2010
  2. Article first published online: 1 JUN 2010
  3. Manuscript Accepted: 12 MAY 2010
  4. Manuscript Received: 2 DEC 2009

Funded by

  • Japan Orthopedics and Traumatology Foundation, Inc.
  • Osaka Cancer Research Foundation
  • Osaka Foundation for the Prevention of Cancer and Cardiovascular Diseases
  • Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation
  • Innovation, Foundation for Promotion of Cancer Research in Japan
  • Ministry of Health, Labor and Welfare, Japan

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Keywords:

  • Synovial sarcoma;
  • SS18-SSX;
  • Cancer initiating ability;
  • Cell of origin;
  • Mesenchymal stem cell

Abstract

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. STEM CELLS 2010;28:1119–1131

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