title: Involvement of oncogenic K-ras on cell migration stimulated by lysophosphatidic acid receptor-2 in pancreatic cancer cells.
abstract: Lysophosphatidic acid (LPA) mediates a variety of cellular responses with atleast six G protein-coupled transmembrane receptors (LPA receptor-1 (LPA(1)-LPA(6))). The interaction between LPA receptors and other cellular molecules on the biological function is not fully understood. Recently, we have reported that LPA(1) suppressed and LPA(3) stimulated cell migration of pancreatic cancer cells. In the present study, to evaluate the function of LPA(2) on motile and invasive activities of pancreatic cancer cells, we generated Lpar2 knockdown (HPD-sh2) cells from hamster pancreatic cancer cells and measured their cell migration ability. In cell motility and invasive assays with an uncoated Cell Culture Insert, HPD-sh2 cells showed significantly lower intrinsic activity than control (HPD-GFP) cells. Since K-ras mutations were frequently detected in pancreatic cancer, we next investigated whether oncogenic K-ras is involved in cell migration induced by LPA(2) using K-ras knockdown (HPD-K2) cells. The cell motile ability of HPD-K2 cells was significantly lower than that of control cells. To confirm LPA(2) increases cell migration activity, cells were pretreated with dioctylglycerol pyrophosphate (DGPP) which is the antagonist of LPA(1)/LPA(3). The cell motile and invasive abilities of DGPP -treated HPD-GFP cells were markedly higher than those of untreated cells, but DGPP did not stimulate cell migration of HPD-K2 cells. These results suggest that cell migration activity of pancreatic cancer cells stimulated by LPA(2) may be enhanced by oncogenic K-ras.
authors.affiliation: Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, Higashiosaka, Osaka, Japan.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Eriko
authors.initials: E
authors.lastname: Tanabe
authors.forename: Ayano
authors.initials: A
authors.lastname: Shibata
authors.forename: Serina
authors.initials: S
authors.lastname: Inoue
authors.forename: Misaho
authors.initials: M
authors.lastname: Kitayoshi
authors.forename: Souta
authors.initials: S
authors.lastname: Okimoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Fukushima
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tsujiuchi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D006224:Cricetinae; D011756:Diphosphates / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D011905:Genes, ras / Q000235:genetics / Q000502:physiology*; D005990:Glycerol / Q000031:analogs & derivatives / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D011756:Diphosphates; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; C408642:diacylglycerol pyrophosphate; D005990:Glycerol; C032881:lysophosphatidic acid