The expression and localization of neutral endopeptidase 24.11/CD10 in human gestational trophoblastic diseases

Neutral endopeptidase 24.11 (NEP)/CD10 is a cell-surface peptidase that hyd rolyzes various bioactive peptides. NEP is distributed in both normal and n eoplastic cells and plays a functional role by modulating cellular response s to peptide substrates. Recently, NEP has been shown to be expressed in no rmal placental trophoblasts, suggesting its physiological role during pregn ancy. In the present study, we investigated the expression of NEP in hyperp lastic and anaplastic trophoblasts in gestational trophoblastic diseases (G TDs). Flow cytometric analysis demonstrated that NEP was expressed in all c horiocarcinoma cell lines examined. The NEP enzyme activity in these cell l ines correlated with cell-surface protein levels and was abolished by the N EP inhibitor phosphoramidon. On immunoblot analysis, NEP protein was detect ed in both hydatidiform mole and choriocarcinoma tissues as a double band o f 95 and 100 kDa similar to that of the normal placental tissues. Immunohis tochemical analysis revealed that NEP was present on syncytiotrophoblasts, while no or very faint NEP immunoreactivity was observed on cytotrophoblast s in the normal placenta. Similarly, NEP in hydatidiform mole and invasive mole was localized on the membrane of syncytiotrophoblasts, but not on hype rplastic cytotrophoblasts. In contrast, in choriocarcinoma, NEP was highly expressed not only on syncytiotrophoblastic cells but also on invading anap lastic cytotrophoblasts. In addition, NEP was also expressed on intermediat e trophoblasts in placental site trophoblastic tumors. In summary, this is the first study demonstrating the expression of NEP/CD10 in GTDs. The diffe rential localization of NEP among various trophoblastic tumors suggests tha t NEP may play a functional role in the regulation of trophoblast transform ation and human chorionic gonadotropin secretion.