Interferon-gamma and lipopolysaccharide stimulation increases matrix metalloproteinase-9 expression and enhances invasion activity in ras/myc-transformed serum-free mouse embryo cells

Authors

  • Yumi Kidachi,

    Corresponding author
    1. Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Aomori University, 2-3-1 Kobata, Aomori 030-0943, Japan
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  • Hideaki Yamaguchi,

    1. Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Aomori University, 2-3-1 Kobata, Aomori 030-0943, Japan
    2. Graduate School of Environmental Sciences, Aomori University, 2-3-1 Kobata, Aomori 030-0943, Japan
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  • Hironori Umetsu,

    1. Laboratory of Food Chemistry, Department of Life Sciences, Junior College, Gifu Shotoku Gakuen University, 1-38 Nakauzura, Gifu 500-8288, Japan
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  • Kazuo Ryoyama

    1. Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Aomori University, 2-3-1 Kobata, Aomori 030-0943, Japan
    2. Graduate School of Environmental Sciences, Aomori University, 2-3-1 Kobata, Aomori 030-0943, Japan
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Corresponding author. Tel.: +81 17 738 2001−5515; fax: +81 17 738 2030. kidachi@aomori-u.ac.jp

Abstract

Ras/myc-transformed serum-free mouse embryo (ras/myc SFME) cells were treated with interferon-gamma (IFN-γ, 100 units/ml) and/or lipopolysaccharide (LPS, 0.5 μg/ml) for 24 h to investigate the effects of these ligands on the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). Aminoguanidine (AG, 1 mM; a nitric oxide synthase [NOS] inhibitor) was also added along with IFN-γ and LPS to analyze a possible association of NO with invasiveness. Treatment of cells with IFN-γ alone did not alter MMP-9 mRNA expression or pro-MMP-9 production, but LPS alone and IFN-γ + LPS co-treatment enhanced them significantly. TIMP-1 mRNA expression remained unchanged with or without treatment and the mRNA expression of MMP-9 exceeded that of TIMP-1 in LPS- or IFN-γ + LPS-treated cells. Co-treatment of cells with IFN-γ and LPS up-regulated invasiveness and indicated a possible involvement of NO in the enhancement of invasiveness. These results suggest that ras/myc SFME cells respond to inflammatory and infectious conditions and that they may possibly modulate their characteristics as cancer cells due to their increase in MMP-9 expression and invasion activity.

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