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SSX : New Molecular Target of Bone and Soft Tissue Tumor

Research Project

Project/Area Number 16591520
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionOsaka Medical Center for Cancer and Cardiovascular Diseases

Principal Investigator

YOSHIOKA Kiyoko  Osaka Medical Center for Cancer and Cardiovascular Diseases, Biology, Chief Investigator, 研究所, 主任研究員 (40342993)

Co-Investigator(Kenkyū-buntansha) ITOH Kazuyuki  Osaka Medical Center for Cancer and Cardiovascular Diseases, Biology, Department Head, 研究所, 部長 (20301806)
YOSHIKAWA Hideki  Osaka University Graduate School of Medicine, Orthopedic Surgery, Professor, 大学院・医学研究科, 教授 (60191558)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsSSX / invasion / osteosarcoma / colony formation / tumor formation / siRNA / cancer / testis antigen / NASBA / tight junction / LC-MS / MS
Research Abstract

The SSX genes were initially identified as fusion partners to the SYT gene in human synovial sarcomas carrying a recurrent t (X;18)(p11.2;q11.2) chromosomal translocation. Besides adult human testis, SSX genes were expressed at varying frequencies in numbers of malignancies thereby categorized as cancer/testis antigens. Using nucleic acid sequence-based amplification, we have reported that the expression level in the malignant tumors (3.8±1.4 copies/μg of total RNA in log10 order) was significantly higher than that in the benign tumors (2.4±0.5,p<0.0001). In order to examine the biological function of SSX, we firstly made stable transfectants with wild type SSX using human osteosarcoma cell line, Saos-2, which moderately expressed SSX. The expression of SSX was mainly localized in the nucleus with patched pattern. The SSX transfectants promoted colony formation in soft agar and tumor formation in nude mice, but showed little change in growth rate in 2D culture. The transfectants also increased motility, chemotaxis and invasiveness using scratch wound assay and Boyden chamber assay. Since the C-terminal region of SSX strongly bound to Histone in the nucleus, we next made stable transfectants with C-terminal deletion mutants of SSX1,using human fibrosarcoma cell line, HT1080, which highly expressed endogenous SSX1. The transfectants showed marked stress fibers and focal adhesions, decreased motility, chemotaxis and invasiveness in vitro, and attenuated tumorigenesis in nude mice. Furthermore, the lowering of the endogenous expression of SSX1 in HT1080 cells by the treatment with specific siRNA markedly decreased chemotaxis, but did not affect cellular proliferation. Collectively, these data suggested that SSX protein regulated several gene expressions leading to the tumor invasion, and could be a new molecular target under clinical setting.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (19 results)

All 2005 2004

All Journal Article (19 results)

  • [Journal Article] Quantification of SSX mRNA expression in human bone and soft tissue tumors using Nucleic Acid Sequence-Based Amplification (NASBA)2005

    • Author(s)
      Naka, N. et al.
    • Journal Title

      J. Mol. Diagn. 7

      Pages: 187-197

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Intrathecal administration of Y-27632, a specific ROCK inhibitor, for rat neoplastic meningitis2005

    • Author(s)
      Nakagawa, H. et al.
    • Journal Title

      Mol. Cancer Res. 3

      Pages: 425-433

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Multiple signaling pathways are activated during Insulin-like growth factor-1 (IGF-1) stimulated breast cancer cell migration2005

    • Author(s)
      Zhang X. et al.
    • Journal Title

      Breast Cancer Res. Treat. 93

      Pages: 159-168

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Quantification of SSX mRNA expression in human bone and soft tissue tumors using Nucleic Acid Sequence-Based Amplification (NASBA)2005

    • Author(s)
      Naka, N., Joyama, S., Tsukamoto, Y., Yoshioka, K., Hashimoto, N., Ujiiye T., Hayashi, T., Kawase, M., Mano, M., Ishiguro, S., Myoui, A., Ueda, T., Yoshikawa, H., Araki, N., Itoh, K.
    • Journal Title

      J.Mol.Diagn. 7

      Pages: 187-197

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Intrathecal administration of Y-2 7632,a specific ROCK inhibitor, for rat neoplastic meningitis2005

    • Author(s)
      Nakagawa, H., Yoshioka, K., Miyahara, E., Fukushima, Y, Tamura, M., Itoh, K.
    • Journal Title

      Mol.Cancer.Res. 3(cited on the cover)

      Pages: 425-433

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Multiple signaling pathways are activated during Insulin-like growth factor-I (IGF-I) stimulated breast cancer cell migration2005

    • Author(s)
      Zhang, X., Lin, M., van Golen, KL, Yoshioka, K., Itoh K., Yee, D.
    • Journal Title

      Breast Cancer Res.Treat. 93

      Pages: 159-168

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Quantification of SSX mRNA expression in human bone and soft tissue tumors using Nucleic Acid Sequence-Based Amplification (NASBA)2005

    • Author(s)
      Naka, N., et al.
    • Journal Title

      J. Mol. Diagn. 7

      Pages: 187-197

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Intrathecal administration of Y-27632, a specific ROCK inhibitor, for rat neoplastic meningitis2005

    • Author(s)
      Nakagawa, H., et al.
    • Journal Title

      Mol. Cancer Res. 3

      Pages: 425-433

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Multiple signaling pathways are activated during Insulin-like growth factor-1(IGF-1) stimulated breast cancer cell migration2005

    • Author(s)
      Zhang X., et al.
    • Journal Title

      Breast Cancer Res. Treat. 93

      Pages: 159-168

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Quantification of SSX mRNA expression in human bone and soft tissue tumors using Nucleic Acid Sequence-Based Amplification (NASBA)2005

    • Author(s)
      Naka, N. et al.
    • Journal Title

      J.Mol.Diagn. (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] LIM kinase 1 : evidence for a role in the regulation of intracellular vesicle trafficking of lysosomes and endosomes in human breast cancer cells2004

    • Author(s)
      Nishimura, Y. et al.
    • Journal Title

      Eur. J. Cell Biol. 83

      Pages: 369-380

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Interleukin-6/soluble Interleukin-6 Receptor Signaling Attenuates Proliferation and Invasion, and Induces Morphological Changes of a Newly Established Pleomorphic Malignant Fibrous Histiocytoma Cell Line2004

    • Author(s)
      Nakanishi, H. et al.
    • Journal Title

      Am. J. Pathol. 165

      Pages: 471-480

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] SSX : new molecular target regulating cancer cell invasion2004

    • Author(s)
      Itoh, K. et al.
    • Journal Title

      Clin. Exp. Metastasis 21

      Pages: 617-617

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] LIM kinase 1: Evidence for a role in the regulation of intracellular vesicle trafficking of lysosomes and endosomes in human breast cancer cells2004

    • Author(s)
      Nishimura, Y., Yoshioka, K., Bernard, O., Himeno, M., Itoh, K.
    • Journal Title

      Eur.J.Cell Biol. 83

      Pages: 369-380

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] IL-6/soluble IL-6R Signaling Attenuates Proliferation and Invasion, and Induces Morphological Changes of a Newly Established Pleomorphic Malignant Fibrous Histiocytoma Cell Line2004

    • Author(s)
      Nakanishi, H.Yoshioka, K., Joyama S., Araki, N., Myoui, A., Ishiguro, S., Ueda, T., Yoshikawa, H., Itoh, K.
    • Journal Title

      Am.J.Pathol. 165

      Pages: 471-480

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] SSX : new molecular target regulating cancer cell invasion2004

    • Author(s)
      Itoh, K., Joyama, S., Naka, N., Yoshioka, K.
    • Journal Title

      Abstracts of the 10th International Congress of the Metastasis Research Society 617

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Interleukin-6/Soluble Interleukin-6 Receptor Signaling Attenuates Proliferation and Invasion, and Induces Morphological Changes of a Newly Established Pleomorphic Malignant Fibrous Histiocytoma Cell Line2004

    • Author(s)
      Nakanishi, H. et al.
    • Journal Title

      Am.J.Pathol. 165

      Pages: 471-480

    • Related Report
      2004 Annual Research Report
  • [Journal Article] LIM kinase 1 : evidence for a role in the regulation of intracellular vesicle trafficking of lysosomes and endosomes in human breast cancer cells2004

    • Author(s)
      Nishimura, Y. et al.
    • Journal Title

      Eur.J.Cell Biol. 83

      Pages: 369-380

    • Related Report
      2004 Annual Research Report
  • [Journal Article] SSX : new molecular target regulating cancer cell invasion2004

    • Author(s)
      Itoh, K. et al.
    • Journal Title

      Clin.Exp.Metastasis 21

      Pages: 617-617

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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