Lysophosphatidic acid (LPA), which interacts with at least three
G protein-coupled receptors (GPCRs), LPA1/Edg-2, LPA2/Edg-4, and LPA3/Edg-7, is a
lipid mediator with diverse effects on various cells. Here, we investigated the expression profiles of
LPA receptors and patterns of LPA-induced migration in
gastric cancer cells. Northern blot analysis revealed that various
gastric cancer cells expressed variable levels of LPA1, LPA2, and LPA3 without a consistent pattern. Using a Boyden chamber assay, LPA markedly increased cell migration of LPA1-expressing cells, the effects of which were almost totally abrogated by
Ki16425, an LPA antagonist against LPA1 and LPA3. In contrast, LPA by itself did not significantly induce migration in MKN28 and MKN74 cells, which exclusively expressed LPA2. However, when
hepatocyte growth factor (HGF) was placed with LPA in the lower chamber, LPA induced migration of these cells in a dose-dependent manner. Immunoprecipitation analysis revealed that LPA induced transient
tyrosine phosphorylation of c-Met in LPA2-expressing cells, which suggests that the transactivation of c-Met by LPA causes a cooperative migratory response with HGF to these cells. Our results indicate that LPA regulates the migration of
gastric cancer cells in a receptor-specific manner and suggest that the expression pattern of
LPA receptors may affect the metastatic behavior of
gastric cancer.