[Mechanism of tumor cell invasion studied by a culture model--modification of invasiveness by host mediators].

A culture model for invasion of rat mesothelial cell layer by rat ascites hepatoma cells has been developed. By using this quantitative model, we have recently found that the invasiveness of tumor cells is not only genetically determined but is greatly influenced by their interactions with host cells and host mediators. The preculture with macrophages was found to enhance both the in vitro and in vivo invasive potentials of the tumor cells. This potentiation appears to be mediated partly by oxygen radicals generated by the cocultured macrophages. The in vitro invasive capacity was also augmented by pretreating the tumor cells with TGF-beta, or with activated platelets. In the in vitro invasion assay system, tumor cells did not invade against cultured mesothelial cell monolayers without fetal calf serum. Serum could be completely substituted by oleoyl-lysophosphatidic acid (LPA) or bacterial phospholipase D (PLD), suggesting a possible participation of particular signaling cascade, PLD-LPA(PA) system, in the invasion of certain tumor cells.