The role of lysophosphatidic acid in cell growth and metastatis.

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To understand the role of lysophosphatidic acid (LysoPA) , first we developed the antibodies against palmitoyl LysoPA,which has saturated fatty acid, and oleoyl LysoPA,which has unsaturated fatty acid. These antibodies are very specific to each phospholipids and have little cross reactivity against other phospholipids such as phosphatidylcholine, phosphatidic acid or lysophosphatidylcholine. We next established the method of LysoPA measurement by TLC-immunostaining. We found LysoPA in serum as the concentration of 3-10 muM by using this method, which is comparable to the concentration of cell growth. These date suggest that LysoPA has some physiological role in cell growth and metastasis.To clarify next the intracellular signaling of LysoPA,we examined the changes of NIH3T3 cells with the treatment of LysoPA.We found that focal adhesion kinase, paxillin and tensin were phosphorylated on tyrosine after LysoPA treatment. These phosphorylation seem to lead the rearrangement of cytoskeletone of these cells, and make them easier to high locomotion and metastasis.