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Lysophosphatidic acid receptor-3 increases tumorigenicity and aggressiveness of rat hepatoma RH7777 cells

Authors

  • Kyoko Okabe,

    1. Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, Higashiosaka, Osaka, Japan
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  • Mai Hayashi,

    1. Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, Higashiosaka, Osaka, Japan
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  • Kohei Kato,

    1. Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, Higashiosaka, Osaka, Japan
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  • Mai Okumura,

    1. Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, Higashiosaka, Osaka, Japan
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  • Rie Fukui,

    1. Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, Higashiosaka, Osaka, Japan
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  • Kanya Honoki,

    1. Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan
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  • Nobuyuki Fukushima,

    1. Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kinki University, Higashiosaka, Osaka, Japan
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  • Toshifumi Tsujiuchi

    Corresponding author
    1. Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, Higashiosaka, Osaka, Japan
    • Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
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  • The authors have no conflict of interest.

Abstract

Lysophosphatidic acid (LPA), which interacts with G protein-coupled transmembrane LPA receptors exhibits several biological effects, such as cell proliferation, migration, and differentiation. Recently, it has been reported that alteration of LPA receptor genes occurs in several cancer cells. In this study, to assess the biological role of LPA receptor-3 (LPA3) in the pathogenesis of tumor cells, we generated the Lpar3-expressing cells (RHa3B12 and RHa3G8) from rat hepatoma RH7777 cells, and examined their abilities of cell migration and tumorigenicity, compared with the Lpar3-unexpressing cells. In cell motility and invasion assays, RHa3B12 and RHa3G8 cells showed significantly higher intrinsic activity without LPA treatment than control RH7777AB cells. LPA treatment further increased cell motility and invasion of these cells. The cell motility of RHa3B12 and RHa3G8 cells stimulated by LPA treatment was significantly suppressed by pretreatment with inhibitors of Gi or Gq proteins. In a soft agar assay, the large sized colonies were formed in RHa3B12 and RHa3G8 cells, but not in RH7777AB cells. The cell survival of RHa3G8 cells treated with cisplatin (CDDP) or doxorubicin (DOX) was higher than that of RH7777AB cells, correlating with the elevated expression levels of multidrug-resistance related genes, Mdr1a, Mdr1b, and Gstp1. These results suggest that LPA3 may be involved in progression and aggressiveness of rat hepatoma RH7777 cells. © 2011 Wiley Periodicals, Inc.

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