Placental leucine aminopeptidase (P-LAP) and glucose transporter 4 (GLUT4) expression in benign, borderline, and malignant ovarian epithelia.
OBJECTIVE
Increased glucose consumption is a characteristic of malignant cells. Glucose is transported into the cell via facilitative glucose transporters, which are known to be members of a supergene family. The insulin-responsive GLUT4 isoform is expressed almost exclusively in insulin target tissues. P-LAP is a cell surface aminopeptidase, and is a synonym for oxytocinase. P-LAP is also referred to as insulin-regulated membrane aminopeptidase (IRAP) associated with GLUT4-containing vesicle. The authors evaluated P-LAP and GLUT4 expression in benign, borderline, and malignant ovarian epithelia.


METHODS
Histologic sections of formalin-fixed, paraffin-embedded specimens from 11 patients with benign serous or mucinous cystadenomas, 14 patients with serous or mucinous borderline tumors, and 80 patients with epithelial-ovarian adenocarcinomas (29 serous, 17 endometrioid, 14 mucinous, and 20 clear cell adenocarcinomas) were stained for P-LAP and GLUT4 using each polyclonal antibody. Expressions of P-LAP and GLUT-4 in ovarian cancer cells were detected by Western blotting.


RESULTS
P-LAP immunoreactivity was detected in 2 of 11 benign cystadenomas. None of the 11 benign ovarian tumors showed any immunoreactivity for GLUT4. Seven of 14 borderline tumors demonstrated P-LAP immunoreactivity, while 5 of 14 borderline tumors demonstrated GLUT4 immunoreactivity. P-LAP was expressed in 23 of 29 in serous, 15 of 17 endometrioid, 13 of 14 mucinous, and all clear-cell adenocarcinomas. The tendency toward increased P-LAP expression with advancing grade was observed in serous adenocarcinomas. GLUT4 was expressed in 13 of 29 serous, 13 of 17 endometrioid, 13 of 14 mucinous, and 18 of 20 clear-cell adenocarcinomas. In invasive carcinomas, there was a direct correlation between P-LAP immunoreactivity and GLUT4 immunoreactivity (correlation coefficient [r] = 0.58; P < 0.01). Furthermore, P-LAP overexpression in SKOV3 cells induced the GLUT4 expression.


CONCLUSIONS
P-LAP and GLUT4 are available not only for the evaluation of ovarian epithelial malignancy, but also as targets for molecular therapy. Further study to investigate the roles of P-LAP and GLUT4 in ovarian carcinoma is needed.
Shibata
Kiyosumi
K
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550, Japan. shiba@med.nagoya-u.ac.jp
Kajiyama
Hiroaki
H
Mizokami
Yayoi
Y
Ino
Kazuhiko
K
Nomura
Seiji
S
Mizutani
Shigehiko
S
Terauchi
Mikio
M
Kikkawa
Fumitaka
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D010122:Cystinyl Aminopeptidase / Q000096:biosynthesis* / Q000235:genetics; D004848:Epithelium / Q000201:enzymology / Q000378:metabolism; D005260:Female; D051275:Glucose Transporter Type 4; D006801:Humans; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness; D010049:Ovarian Diseases / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495692:SLC2A4 protein, human; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase