title: Hepatoma cell migration through a mesothelial cell monolayer is inhibited by cyclic AMP-elevating agents via a Rho-dependent pathway.
abstract: 1-Oleoyl lysophosphatidic acid (LPA) induces transmonolayer migration (in vitro invasion) of rat ascites hepatoma MM1 cells and their morphological changes leading to the migration. We have previously shown that an LPA analog, palmitoyl cyclic phosphatidic acid (Pal-cPA), suppresses transmonolayer migration of MM1 cells by rapidly increasing the intracellular cyclic AMP (cAMP) concentration. We report here that various cAMP-elevating agents, including dibutyryl cAMP, forskolin, cholera toxin and 3-isobutyl-1-methylxanthine, consistently inhibited LPA-induced transmonolayer migration of MM1 cells. Moreover, pull-down assays for GTP-bound, active RhoA demonstrated that the blockage by cAMP-elevating agents of morphological changes leading to the migration was probably mediated through inhibiting RhoA activation.
authors.affiliation: Department of Tumor Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. mmukai@mail.mc.pref.osaka.jp
authors.forename: M
authors.initials: M
authors.lastname: Mukai
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Tatsuta
authors.forename: T
authors.initials: T
authors.lastname: Iwasaki
authors.forename: A
authors.initials: A
authors.lastname: Togawa
authors.forename: F
authors.initials: F
authors.lastname: Imamura
authors.forename: H
authors.initials: H
authors.lastname: Akedo
mesh_terms: D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism*; D004347:Drug Interactions; D004848:Epithelium / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology*; D008246:Lysophospholipids / Q000494:pharmacology*; D018301:Neoplasms, Mesothelial / Q000473:pathology; D051381:Rats; D014407:Tumor Cells, Cultured; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D003994:Bucladesine; D000242:Cyclic AMP; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; C032881:lysophosphatidic acid