We recently identified two novel
aminopeptidases,
placental leucine aminopeptidase (P-LAP) and adipocyte-derived
leucine aminopeptidase (A-LAP). Enzymatically, P-LAP degrades
oxytocin,
vasopressin, and
angiotensin III, while A-LAP degrades
angiotensin II and
kallidin. In this study we investigated the expression and localization of P-LAP and A-LAP in human trophoblastic cells in the normal placenta (n = 26), gestational
choriocarcinoma (n = 8), and
placental site trophoblastic tumor (n = 3). On immunoblot analysis both P-LAP and A-LAP
proteins were detected in normal placenta and five
choriocarcinoma tissues, as well as in two
choriocarcinoma cell lines. Immunohistochemical staining of normal placental tissues demonstrated that P-LAP was not only localized in villous syncytiotrophoblasts but also highly expressed in extravillous trophoblasts (EVTs) invading the decidua or maternal spiral arteries. The expression level of P-LAP on these invasive EVTs reached a maximum during the late first to second trimesters of pregnancy, and it decreased in the third trimester. Similarly, A-LAP was strongly expressed in EVTs invading the decidua or spiral arteries in the second trimester of pregnancy, while it was weakly or moderately expressed in villous cytotrophoblasts or EVTs located in the cell columns. These two
aminopeptidases were more strongly expressed in all eight
choriocarcinomas and three
placental site trophoblastic tumors and mainly localized to the intermediate-type
trophoblastic tumor cells invading the uterine myometrium or stromal vessels. In summary P-LAP and A-LAP were predominantly expressed in the invasive phenotype of EVTs during placentation, as well as in the invasive
tumor cells of
trophoblastic neoplasms. These results suggest the involvement of these
aminopeptidases in invasiveness of both normal and malignant intermediate-type trophoblasts possibly through degradation of specific
peptide substrates.