Cooperation of fibronectin with lysophosphatidic acid induces motility andtranscellular migration of rat ascites hepatoma cells

We have previously shown that the transcellular migration of rat ascites he patoma (AH130-MM1) cells through a cultured mesothelial cell monolayer (MCL ) is triggered with lysophosphatidic acid (LPA) that stimulates actin polym erization and myosin light chain phosphorylation through the activation of Rho-ROCK (Rho-kinase) cascade. When, however, the motility of MM1 cells on a glass surface was tested by phagokinetic track motility assay, LPA failed to induce the motility. Nevertheless, when the glass had been coated with fibronectin (FN), LPA could induce phagokinetic motility which was accompan ied by transformation of MM1 cells to fusiform-shape and assembly of focal adhesion. beta 1 integrin, the counter receptor of FN, was expressed on MM1 cells. Anti-FN antibody, anti-beta 1 integrin antibody and cyclo-GRGDSPA r emarkably suppressed LPA-induced phagokinetic motility. These antibodies su ppressed LPA-induced transcellular migration through MCL, as well. These re sults indicate that actin polymerization and phosphorylation of myosin ligh t chain through Rho activation are insufficient for inducing motility but t he cooperative FN/beta 1 integrin-mediated adhesion is necessary for both t he phagokinetic motility and transcellular migration of MM1 cells. (C) 2000 Elsevier Science B.V. All rights reserved.