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.

中文翻译：

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胎盘亮氨酸氨肽酶和脂肪细胞来源的亮氨酸氨肽酶在人正常和恶性侵袭性滋养细胞中的表达。

我们最近发现了两种新型氨肽酶，胎盘亮氨酸氨肽酶 (P-LAP) 和脂肪细胞衍生的亮氨酸氨肽酶 (A-LAP)。在酶促作用下，P-LAP 降解催产素、加压素和血管紧张素 III，而 A-LAP 降解血管紧张素 II 和激肽。在这项研究中，我们研究了 P-LAP 和 A-LAP 在正常胎盘 (n = 26)、妊娠绒毛膜癌 (n = 8) 和胎盘部位滋养细胞肿瘤 (n = 3) 中人滋养细胞中的表达和定位。在免疫印迹分析中，P-LAP 和 A-LAP 蛋白均在正常胎盘和五个绒毛膜癌组织以及两个绒毛膜癌细胞系中检测到。正常胎盘组织的免疫组织化学染色表明，P-LAP 不仅定位于绒毛合体滋养细胞，而且在侵入蜕膜或母体螺旋动脉的绒毛外滋养细胞 (EVT) 中也有高表达。P-LAP 在这些侵入性 EVT 上的表达水平在妊娠早期至妊娠中期达到最大值，并在妊娠晚期下降。同样，A-LAP 在妊娠中期侵入蜕膜或螺旋动脉的 EVT 中强烈表达，而在位于细胞柱中的绒毛细胞滋养层或 EVT 中弱或中度表达。这两种氨肽酶在所有八种绒毛膜癌和三种胎盘部位滋养细胞肿瘤中均有更强的表达，主要定位于侵入子宫肌层或间质血管的中间型滋养细胞肿瘤细胞。总之，P-LAP 和 A-LAP 主要在胎盘形成过程中 EVT 的侵袭性表型以及滋养细胞肿瘤的侵袭性肿瘤细胞中表达。这些结果表明这些氨肽酶可能通过特定肽底物的降解参与正常和恶性中间型滋养细胞的侵袭。