Expression of aminopeptidase A in human gestational choriocarcinoma cell lines and tissues.
Aminopeptidase A (AP-A), a cell-surface metallopeptidase hydrolyzing peptide with N-terminal acidic residues, has been proved to be identical to the B cell differentiation antigen BP-1 and to the kidney differentiation antigen 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 present study, we examined the expression and enzymatic activity of AP-A in human gestational choriocarcinoma, a neoplastic transformant from trophoblasts which comprises a heterogenous population of trophoblastic cells in different stages of differentiation. Flow cytometry and immunoblot analysis demonstrated that AP-A was expressed in five choriocarcinoma cell lines which were secreting low or moderate levels 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 abrogated by amastatin, an inhibitor of AP-A. Immunohistochemical analysis revealed that AP-A was present in seven of eight choriocarcinoma tissues and was localized on the cell membrane of cytotrophoblastic choriocarcinoma cells, but not on cells with syncytiotrophoblast-like features. These results demonstrate that AP-A is expressed on most choriocarcinomas and its expression is restricted to low hCG-secreting, cytotrophoblastic cells and down-regulated as a function of cell differentiation, suggesting an involvement of AP-A in the differentiation/maturation process of neoplastic trophoblasts.
Ino
K
K
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan.
Nagasaka
T
T
Okamoto
T
T
Uehara
C
C
Nakazato
H
H
Nakashima
N
N
Mizutani
S
S
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D002822:Choriocarcinoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D006063:Chorionic Gonadotropin / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D043384:Glutamyl Aminopeptidase; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008969:Molecular Sequence Data; D011247:Pregnancy; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology
D000911:Antibodies, Monoclonal; D006063:Chorionic Gonadotropin; D004791:Enzyme Inhibitors; D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase