Yamamoto Yasuko, Hirakawa Eiichiro, Mori Seiji, Hamada Yoshinosuke, Kawaguchi Naomasa, Matsuura Nariaki
Department of Molecular Pathology, Graduate School of Medicine and Health Sciences, Osaka University, Japan.
Biochem Biophys Res Commun. 2005 Jul 22;333(1):223-9. doi: 10.1016/j.bbrc.2005.05.084.
Carcinoembryonic antigen (CEA), a widely used tumor marker, is attached by a glycosylphosphatidylinositol (GPI) anchor motif to the cell membrane. Recent study suggested that membrane-bound CEA might be cleaved by glycosylphosphatidylinositol-phospholipase D (GPI-PLD). We studied the effect of GPI-PLD on the cleavage of CEA to elucidate the implication for metastatic potential in colorectal carcinoma cells. CEA amount of conditioned medium was changed by suramin and phenanthroline (activator and inhibitor of GPI-PLD) only in SW620 and SW837 which expressed both CEA and GPI-PLD mRNA. Suramin treatment also augmented migratory activity and decreased cell surface CEA expression in SW620 and SW837. Furthermore, GPI-PLD knockdown cells using GPI-PLD-specific siRNA in SW620 and SW837 showed decreased CEA secretion from cell membrane and the migration activity, increased membrane-bound CEA amount. Splenic injection of SW620 and SW837 induced marked hepatic metastases in nude mice. These results suggest that membrane-bound CEA is cleaved by GPI-PLD and that this cleavage enhances the metastatic potential in colorectal carcinoma cells.
癌胚抗原（CEA）是一种广泛应用的肿瘤标志物，通过糖基磷脂酰肌醇（GPI）锚定基序附着于细胞膜。最近的研究表明，膜结合型CEA可能被糖基磷脂酰肌醇磷脂酶D（GPI-PLD）裂解。我们研究了GPI-PLD对CEA裂解的影响，以阐明其对结肠癌细胞转移潜能的影响。仅在同时表达CEA和GPI-PLD mRNA的SW620和SW837细胞中，苏拉明和菲咯啉（GPI-PLD的激活剂和抑制剂）改变了条件培养基中的CEA量。苏拉明处理还增强了SW620和SW837细胞的迁移活性并降低了细胞表面CEA的表达。此外，在SW620和SW837细胞中使用GPI-PLD特异性siRNA敲低GPI-PLD后，细胞膜CEA分泌减少，迁移活性降低，膜结合型CEA量增加。向裸鼠脾脏注射SW620和SW837细胞可诱导明显的肝转移。这些结果表明，膜结合型CEA被GPI-PLD裂解，并且这种裂解增强了结肠癌细胞的转移潜能。
