Lysophosphatidic Acid (LPA) Stimulates the Migration of Gastric Cancer Cells with Two Distinct Mechanisms

摘要

Lysophosphatidic acid (LPA), which interacts with at least three G protein-coupled receptors, LPAl/Edg-2, LPA2/Edg-4, and LPA3/Edg-7, is a lipid mediator with diverse effects on various cells. Nothernblot analysis showed that MKN1, NUGC-3, AZ521, HGC-27, and GCIY, preferentially expressed LPA1, whereas MKN28, MKN45, MKN74 and KATO HI expressed LPA2 exclusively. Using a Boyden chamber assay, LPA markedly increased cell migration of LPA1 expressing cells, but not of LPA2 expressing cells. However, when hepatocyte growth factor (HGF) was placed with LPA in the lower chamber, LPA strongly augmented migration of LPA2 expressing cells. Immunoprecipitation revealed LPA induce transient tyrosine phos-phorylation of the c-met in MKN28, suggesting the transactivation of c-met by LPA. Our results indicate that LPA regulates migration and metastatic potential of gastric cancer in receptor specific manner.