Serum osteopontin, an enhancer of tumor metastasis to bone, promotes B16 melanoma cell migration

Authors

  • Chikako Hayashi,

    1. Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 101-0062, Japan
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  • Susan Rittling,

    1. The Forsyth Institute, Boston, Massachusetts
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  • Tadayoshi Hayata,

    1. Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 101-0062, Japan
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  • Teruo Amagasa,

    1. Department of Maxillofacial surgery, Tokyo Medical and Dental University, Tokyo, Japan
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  • David Denhardt,

    1. Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersy
    2. 21st Century Center of Excellence Program for the Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo, Japan
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  • Yoichi Ezura,

    Corresponding author
    1. Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 101-0062, Japan
    • Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 3-10 Kanda-Surugadai, 2-chome Chiyoda-ku, Tokyo 101-0062, Japan.
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  • Kazuhisa Nakashima,

    1. Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 101-0062, Japan
    2. 21st Century Center of Excellence Program for the Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo, Japan
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  • Masaki Noda

    Corresponding author
    1. Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 101-0062, Japan
    2. 21st Century Center of Excellence Program for the Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo, Japan
    3. Core to Core Program, JSPS, Tokyo Medical and Dental University, Tokyo, Japan
    4. Hard Tissue Genome Research Center, Tokyo Medical and Dental University, Tokyo, Japan
    • Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 3-10 Kanda-Surugadai, 2-chome Chiyoda-ku, Tokyo 101-0062, Japan.
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Abstract

Tumor malignancy is associated with several features such as proliferation ability and frequency of metastasis. Since tumor metastasis shortens patients' lifetime, establishment of therapy for anti-metastasis is very important. Osteopontin (OPN), which abundantly expressed in bone matrix, is involved in cell adhesion, migration, extracellular matrix (ECM) invasion and cell proliferation via interaction with its receptor, that is, αvβ3 integrin. OPN is believed to be a positive regulator of tumor metastasis in vivo. However, how OPN regulates metastasis is largely unknown. Here, we explore the role of OPN in cell migration. Serum from wild-type mice induced cell migration of B16 melanoma cells, while serum from OPN-deficient mouse suppressed this event. The presence of recombinant OPN significantly enhanced cell migration compared to albumin containing medium. OPN-induced cell migration was suppressed by inhibiting the ERK/MAPK pathway indicating that OPN-induced cell migration depends on this pathway. Overexpression of OPN in these cancer cells per se promoted cell proliferation and tended to increase B16 cell migration suggesting that OPN promotes bone metastasis by playing dual roles both in host microenvironment and in tumor cell itself. In conclusion, the elevated OPN expression in host tissue and tumor cell itself promotes tumor cell migration reading to tumor metastasis, suggesting that neutralization of OPN-induced signal might be effective in suppression of tumor metastasis. J. Cell. Biochem. 101: 979–986, 2007. © 2007 Wiley-Liss, Inc.

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