Inhibition of APN/CD13 leads to suppressed progressive potential in ovarian carcinoma cells.
BACKGROUND
Aminopeptidase N (APN/CD13), a 150-kDa metalloprotease, is a multifunctional cell surface aminopeptidase with ubiquitous expression. Recent studies have suggested that APN/CD13 plays an important role in tumor progression of several human malignancies. In the current study, we investigated the role of APN/CD13 in ovarian carcinoma (OVCA) progression.


METHODS
We first examined the expression of APN/CD13 at the protein level in a variety of OVCA cell lines and tissues. We subsequently investigated whether there was a correlation between APN/CD13 expression and invasive potential of various OVCA cell lines. Moreover, we investigated the function of APN/CD13 in OVCA cells using bestatin, an APN/CD13 inhibitor, or transfection of siRNA for APN/CD13.


RESULTS
We confirmed that APN/CD13 was expressed in OVCA tissues and cell lines to various extents. There was a positive correlation between APN/CD13 expression and migratory potential in various OVCA cell lines with accordingly enhanced secretion of endogenous MMP-2. Subsequently, we found a significant decrease in the proliferative and migratory abilities of OVCA cells after the addition of bestatin or the inhibition of APN/CD13 expression by siRNA. Furthermore, in an animal model, daily intraperitoneal administration of bestatin after inoculation of OVCA cells resulted in a decrease of peritoneal dissemination and in prolonged survival of nude mice.


CONCLUSIONS
The current data indicate the possible involvement of APN/CD13 in the development of OVCA, and suggest that clinical use of bestatin may contribute to better prognosis for ovarian carcinoma patients.
Terauchi
Mikio
M
Department of Obstetrics and Gynecology, Nagoya University, Graduate School of Medicine, Tsuruma-cho 65, Showa-ku, Nagoya 466-8550, Japan. mikio727@med.nagoya-u.ac.jp
Kajiyama
Hiroaki
H
Shibata
Kiyosumi
K
Ino
Kazuhiko
K
Nawa
Akihiro
A
Mizutani
Shigehiko
S
Kikkawa
Fumitaka
F
D000818:Animals; D018826:CD13 Antigens / Q000037:antagonists & inhibitors* / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000473:pathology / Q000628:therapy*
D018826:CD13 Antigens; D020778:Matrix Metalloproteinase 2; D007930:Leucine; C012211:ubenimex