Translocation of lysophosphatidic acid phosphatase in response to gonadotropin-releasing hormone to the plasma membrane in ovarian cancer cell

Objective: Lysophosphatidic acid mediates proliferative and/or morphologic effects on multiple cell lineages, which include ovarian cancer cells. Lysophosphatidic acid hydrolysis limits the duration of lysophosphatidic acid's action. We examined hormonal translocation of lipid phosphate phosphatase type 3 to the plasma membrane in gonadotropin-releasing hormone-responsive ovarian cancers. Study design: Ovarian cancers that were removed surgically and the ovarian cancer cell lines Caov-3 and SK-OV-3 were examined. Lipid phosphate phosphatase type 3 protein and activity in plasma membranes were assessed by immunohistochemical staining with lipid phosphate phosphatase type 3-specific antibodies and by the measurement of the conversion of exogenous [H-3-oleoyl]lysophosphatidic acid to mono [H-3-oleoyl] glycerol, respectively. Results: In ovarian cancers that were removed surgically, the cell surface staining and activity measurements indicated that a portion of the enzyme was localized to the plasma membrane. In Caov-3 cells and SK-OV-3 cells, lipid phosphate phosphatase type 3 protein was present both in the cytoplasm and at the plasma membrane. Treatment of the cells with a gonadotropin-releasing hormone agonist buserelin produced a rapid and progressive translocation of lipid phosphate phosphatase type 3 protein to the plasma membrane, with a concomitant loss of cytoplasmic staining. The enzyme activity in plasma membrane was also increased when the cell lines were exposed to the gonadotropin- releasing hormone agonist in intact cells before the assay of the cell membranes. Conclusion: These findings support the presence of lipid phosphate phosphatase type 3 in plasma membrane of ovarian cancers and provide for the ability of agonists (such as gonadotropin-releasing hormone) to induce the translocation of lipid phosphate phosphatase type 3 to plasma membrane in ovarian cancer cells. (C) 2004 Elsevier Inc. All rights reserved.