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Despite the consistent finding of upregulated prostate specific membrane antigen (PSMA) with increased prostate cancer (PCa) aggressiveness, the functional role of PSMA in PCa is unknown. Recently, it was reported that suppression of PSMA expression increases invasiveness, and expression of inactivating PSMA mutants reduces invasiveness. In this study, using in vitro cell model systems and live-cell imaging methods, we characterized the role of PSMA in cell motility and adhesion. We demonstrated, using wound-healing assay, that PSMA expression reduces cell motility when compared with control PSMA-negative PCa cells. Six hours after wounding, significant numbers of PSMA-negative cells migrating into the wounded area could be observed. In contrast, limited migration was observed in cells expressing PSMA. We also found enhanced PCa cell motility in cells when the PSMA enzymatic activity was inhibited by a specific anti-PSMA antibody. When live cell motility was recorded, the number of PSMA-positive LNCaP cells migrating into the wounded area was almost 2-fold higher in the presence of the inhibitory antibody than control LNCaP cells in the absence of the antibody. No difference in the number of the PSMA-negative PC3 cell migration was observed with or without the application of the inhibitory antibody. More interestingly, we found that expression of PSMA results in morphologically better-spreading PCa cells with redistributed F-actin filaments that regulate cell adhesion and motility. Since the progression of PCa is a multi-stage process that requires repeated adhesion to and detachment from the extracellular matrix microenvironment, our results suggest that PSMA may play a role in PCa adhesion and migration during PCa metastasis.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]