title: Enhanced cellular functions through induction of LPA2by cisplatin in fibrosarcoma HT1080 cells.
abstract: Lysophosphatidic acid (LPA) is a simple biophysical lipid which interacts with at least six subtypes of G protein-coupled LPA receptors (LPA1-LPA6). In cancer cells, LPA signaling via LPA receptors is involved in the regulation of malignant properties, such as cell growth, motility, and invasion. The aim of this study was to assess whether LPA receptors regulate cellular functions of fibrosarcoma cells treated with anticancer drug. HT1080 cells were maintained by the stepwise treatment of cisplatin (CDDP) at a range of 0.01 to 1.0 µM for approximately 6 months. The cell motile and invasive activities of long-term CDDP-treated (HT-CDDP) cells were significantly stimulated by LPA treatment, while HT-CDDP cells in the static state showed the low cell motile and invasive activities in comparison with HT1080 cells. Since the expression level of LPAR2 gene was markedly elevated in HT-CDDP cells, LPA2knockdown cells were generated from HT-CDDP cells. The cell motile and invasive activities of HT-CDDP cells were reduced by LPA2knockdown. In colony assay, large-sized colonies formed by long-term CDDP treatment were suppressed by LPA2knockdown. In addition, LPA2knockdown cells reduced LPA production by autotaxin (ATX), correlating with ATX expression level. These results suggest that LPA signaling via LPA2may play an important role in the regulation of cellular functions in HT1080 cells treated with CDDP.
authors.affiliation: Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiōsaka, Osaka, 577-8502, Japan.
authors.forename: Kaede
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiōsaka, Osaka, 577-8502, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Fukushima
authors.affiliation: Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiōsaka, Osaka, 577-8502, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Fukushima
authors.affiliation: Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan.
authors.forename: Kanya
authors.initials: K
authors.lastname: Honoki
authors.affiliation: Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiōsaka, Osaka, 577-8502, Japan. ttujiuch@life.kindai.ac.jp.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tsujiuchi
mesh_terms: D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D005354:Fibrosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010727:Phosphoric Diester Hydrolases / Q000096:biosynthesis / Q000235:genetics; D049368:Receptors, Lysophosphatidic Acid / Q000096:biosynthesis* / Q000235:genetics; D000099189:Lysophospholipase D
chemical_list: D002945:Cisplatin; D009363:Neoplasm Proteins; D010727:Phosphoric Diester Hydrolases; D049368:Receptors, Lysophosphatidic Acid; D000099189:Lysophospholipase D
keywords: Cell migration; Cisplatin; Fibrosarcoma; LPA; LPA2