title: LPA signaling through LPA receptors regulates cellular functions of endothelial cells treated with anticancer drugs.
abstract: Lysophosphatidic acid (LPA) signaling via LPA receptors provides a variety of cellular functions, including angiogenesis. In this study, to assess an involvement of LPA receptors in cell motile activities of endothelial cells during chemotherapy, F-2 cells were treated with cisplatin (CDDP) and doxorubicin (DOX) at a concentration of 0.01 μM every 24 h for at least 1 month. The treatment of CDDP and DOX inhibited the expression levels of the LPA receptor-1 (Lpar1), Lpar2, and Lpar3 genes in F-2 cells. The cell motile activities of CDDP and DOX treated cells were relatively lower than those of untreated cells. Next, we investigated whether cancer cells could stimulate the cell motile activities of F-2 cells treated with CDDP and DOX. For cell motility assay, CDDP- and DOX-treated cells were co-cultured with pancreatic cancer PANC-1 cells. The cell motile activities of CDDP- and DOX-treated cells were significantly enhanced by the existence of PANC-1 cells, correlating with the LPA receptor expressions. In addition, the elevated cell motile activities were suppressed by the pretreatment of an autotaxin inhibitor S32826. These results suggest that LPA signaling via LPA receptors may regulate the cell motile activities of F-2 cells treated with anticancer drugs.
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka, 577-8502, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Mori
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka, 577-8502, Japan.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Araki
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka, 577-8502, 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, 3-4-1, Kowakae, Higashiosaka, Osaka, 577-8502, 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, 3-4-1, Kowakae, Higashiosaka, Osaka, 577-8502, 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, 3-4-1, Kowakae, Higashiosaka, Osaka, 577-8502, 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, 3-4-1, Kowakae, Higashiosaka, Osaka, 577-8502, 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, 3-4-1, Kowakae, Higashiosaka, Osaka, 577-8502, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Fukushima
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka, 577-8502, Japan. ttujiuch@life.kindai.ac.jp.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tsujiuchi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D018920:Coculture Techniques; D004317:Doxorubicin / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology / Q000473:pathology; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D004317:Doxorubicin; C032881:lysophosphatidic acid; D002945:Cisplatin
keywords: Anticancer drugs; Cell motility; Endothelial cells; LPA receptor; Lysophosphatidic acid