Expression of Placental Leucine Aminopeptidase and Adipocyte-Derived Leucine Aminopeptidase in Human Normal and Malignant Invasive Trophoblastic Cells

Kazuhiko Ino, Fumitaka Kikkawa, Takahiro Suzuki, Hiroaki Kajiyama, Kiyosumi Shibata, Seiji Nomura, Atsuo Itakura, Mitsuaki Ito, Tetsuro Nagasaka, Akira Hattori, Masafumi Tsujimoto, Shigehiko Mizutani

研究成果: Article査読

20 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1799-1809
ページ数11
ジャーナルLaboratory Investigation
83
12
DOI
出版ステータスPublished - 12-2003
外部発表はい

All Science Journal Classification (ASJC) codes

  • 病理学および法医学
  • 分子生物学
  • 細胞生物学

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