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Cold shock domain protein A (CSDA) overexpression inhibits tumor growth and lymph node metastasis in a mouse model of squamous cell carcinoma

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Abstract

Cancer cells metastasize by entering the lymphatic system. Regional lymph-node dissemination is the first detectable step in the metastasis of oral squamous cell carcinoma (SCC) and is highly correlated to the prognosis of the disease. Cold shock domain protein A (CSDA) is a DNA-binding protein that represses angiogenesis and lymphangiogenesis by directly binding to hypoxia response element (HRE) and serum response element (SRE). In our study we used the cell line NR-S1M, a mouse SCC model with a high rate of lymph-node metastasis. Into these cells we transfected the expression-plasmid coding for full-length mouse CSDA. Of importance, we showed that overexpression of CSDA significantly inhibits the production of VEGF-A and VEGF-C in NR-S1M cells. The overexpression of CSDA in NR-S1M cells inhibited tumor growth, inhibited regional lymph-node metastasis, and reduced the density of blood vessels and lymphatic vessels in the primary tumors in vivo. Our results support the hypothesis that VEGF-A and VEGF-C are crucial regulators of angiogenesis and lymphangiogenesis in NR-S1M cells. Therefore, they are promising targets for CSDA overexpression gene therapy to inhibit tumor growth and lymph-node metastasis in SCC.

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Acknowledgments

The Ministry of Education, Culture, Sports, Science and Technology of Japan supported this work with a Grant-in-Aid for the High-Tech Research Center Project.

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Kanagawa Dental College, 82 Inaoka, Yokosuka, Kanagawa, 238-8580, Japan

    Goichi Matsumoto, Yasushi Omi & Ushaku Lee

  2. Department of Biochemistry and Molecular Biology, Kanagawa Dental College, Yokosuka, Japan

    Nobuyuki Yajima

  3. Department of Surgery, Asahikawa Medical University, Asahikawa, Japan

    Hiroyuki Saito

  4. Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan

    Hironori Nakagami & Yasufumi Kaneda

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  1. Goichi Matsumoto
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  2. Nobuyuki Yajima
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  3. Hiroyuki Saito
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  4. Hironori Nakagami
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  5. Yasushi Omi
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  6. Ushaku Lee
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  7. Yasufumi Kaneda
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Correspondence to Goichi Matsumoto.

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Matsumoto, G., Yajima, N., Saito, H. et al. Cold shock domain protein A (CSDA) overexpression inhibits tumor growth and lymph node metastasis in a mouse model of squamous cell carcinoma. Clin Exp Metastasis 27, 539–547 (2010). https://doi.org/10.1007/s10585-010-9343-y

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  • DOI: https://doi.org/10.1007/s10585-010-9343-y

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