Expression of aminopeptidase A in human gestational choriocarcinoma cell lines and tissues

Aminopeptidase A (AP-A), a cell-surface metallopeptidase hydrolyzing peptid e with N-terminal acidic residues, has been proved to be identical to the B cell differentiation antigen BP-I and to the kidney differentiation antige n gp160, suggesting recognition of AP-A as a differentiation-related marker on certain normal and transformed cells. AP-A has also been purified from human placenta and been shown to be localized in the trophoblasts. In the p resent study, we examined the expression and enzymatic activity of AP-A in human gestational choriocarcinoma, a neoplastic transformant from trophobla sts which comprises a heterogenous population of trophoblastic cells in dif ferent stages of differentiation. Flow cytometry and immunoblot analysis de monstrated that AP-A was expressed in five choriocarcinoma cell lines which were secreting low or moderate levers of human chorionic gonadotropin (hCG ), while two high hCG-secreting cell lines lacked AP-A expression. The AP-A enzymatic activity correlated with cell-surface levels of AP-A and was abr ogated by amastatin, an inhibitor of AP-A. Immunohistochemical analysis rev ealed that AP-A was present in seven of eight choriocarcinoma tissues and w as localized on the cell membrane of cytotrophoblastic choriocarcinoma cell s, but not on cells with syncytiotrophoblast-like features. These results d emonstrate that AP-A is expressed on most choriocarcinomas and its expressi on is restricted to low hCG-secreting, cytotrophoblastic cells and down-reg ulated as a function of cell differentiation, suggesting an involvement of AP-A in the differentiation/maturation process of neoplastic trophoblasts. (C) 2000 Harcourt Publishers Ltd.