Novel Role of Prostate-Specific Membrane Antigen in Prostate Cancer Invasion and Metastasis

摘要

Prostate Specific Membrane Antigen, PSMA is a type II transmembrane glycoprotein, overexpressed in prostate carcinoma (PCa) including androgen sensitive and independent disease, increased in expression with early relapse following therapy. PSMA is a carboxypeptidase with two important enzymatic functions, namely, folate hydrolase and NAALADase. We have used in vitro invasion assays to explore the possible role of PSMA in PCa cells. Androgen dependent PCa lines, which express PSMA endogenously (e.g., LNCaP, CWR22) are less invasive compared to androgen independent PSMA negative PC3 or DU145 cells. Ectopic expression of PSMA in PC3 cells reduced the invasiveness of these cells, suggesting that this reduction in the invasion capability of PSMA expressing cells is due to PSMA expression, not due to intrinsic properties of different cell lines. Expression of PSMA mutants lacking carboxypeptidase activity reduced the impact of PSMA expression on invasiveness. Thus it appears that the enzymatic activity is associated with PSMA's effect on cellular invasiveness. To test our experimental results in vivo, we have further co- expressed PSMA and luciferase reporter gene in highly invasive PC3MM2 lines. We obtained several expressors with high luciferase and PSMA expression. Tumor formation ability and metastatic potential of these lines will be tested in mice.