The role of lysophosphatidic acid in cell growth and metastatis.

为了了解溶血磷脂酸（LysoPA）的作用，我们首先开发了针对棕榈酰LysoPA（具有饱和脂肪酸）和油酰LysoPA（具有不饱和脂肪酸）的抗体。这些抗体对每种磷脂都有很强的特异性，对其他磷脂如磷脂酰胆碱、磷脂酸或溶血磷脂酰胆碱几乎没有交叉反应性。我们接下来建立了通过TLC-免疫染色测量LysoPA的方法。通过使用该方法，我们发现血清中LysoPA的浓度为3-10 μ M，这与细胞生长的浓度相当。为了进一步阐明LysoPA在细胞内的信号转导作用，我们研究了LysoPA作用后NIH 3 T3细胞的变化，发现LysoPA作用后，黏着斑激酶、桩蛋白和张力蛋白酪氨酸磷酸化。这些磷酸化可能导致这些细胞的胞浆蛋白重排，使其更容易向高迁移和转移。

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.