title: Different induction of LPA receptors by chemical liver carcinogens regulates cellular functions of liver epithelial WB-F344 cells.
abstract: Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA1to LPA6) mediates a variety of cellular functions, including cell motility. In the present study, we investigated the effects of LPA receptors on cell motile activity during multi-stage hepatocarcinogenesis in rat liver epithelial WB-F344 cells treated with chemical liver carcinogens. Cells were treated with a initiator (N-nitrosodiethylamine (DEN)) and three promoters (phenobarbital (PB), okadaic acid (OA) and clofibrate) every 24 h for 2 days. Cell motile activity was elevated by DEN, correlating with Lpar3 expression. PB, OA, and clofibrate elevated Lpar1 expression and inhibited cell motile activity. To evaluate the effects of long-term treatment on cell motility, cells were treated with DEN and/or PB for at least 6 months. Lpar3 expression and cell motile activity were significantly elevated by the long-term DEN treatment with or without further PB treatment. In contrast, long-term PB treatment with or without further DEN elevated Lpar1 expression and inhibited cell motility. When the synthesis of extracellular LPA was blocked by a potent ATX inhibitor S32826 before cell motility assay, the cell motility induced by DEN and PB was markedly suppressed. These results suggest that activation of the different LPA receptors may regulate the biological functions of cells treated with chemical carcinogens. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kinki University, Kowakae, Higashiosaka, Osaka, Japan.
authors.forename: Miku
authors.initials: M
authors.lastname: Hirane
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kinki University, Kowakae, Higashiosaka, Osaka, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Ishii
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kinki University, Kowakae, Higashiosaka, Osaka, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Tomimatsu
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kinki University, Kowakae, Higashiosaka, Osaka, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Fukushima
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kinki University, Kowakae, Higashiosaka, Osaka, Japan.
authors.forename: Kaede
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kinki University, Kowakae, Higashiosaka, Osaka, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Fukushima
authors.affiliation: Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Kanya
authors.initials: K
authors.lastname: Honoki
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kinki University, Kowakae, Higashiosaka, Osaka, Japan. ttujiuch@life.kindai.ac.jp.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tsujiuchi
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002994:Clofibrate / Q000009:adverse effects / Q000494:pharmacology; D004052:Diethylnitrosamine / Q000009:adverse effects*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism*; D019319:Okadaic Acid / Q000009:adverse effects / Q000494:pharmacology; D010634:Phenobarbital / Q000009:adverse effects / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D049368:Receptors, Lysophosphatidic Acid; D019319:Okadaic Acid; D004052:Diethylnitrosamine; D002994:Clofibrate; D010634:Phenobarbital
keywords: LPA receptor; cell motility; hepatocarcinogenesis; liver carcinogen