Properties of L-type amino acid transporter 1 in epidermal ovarian cancer.
OBJECTIVE
To investigate the expression and the functional properties of L-type amino acid transporter 1 (LAT1) in human epithelial ovarian cancer to provide a basis for potential new therapies to control the growth and the metastasis of ovarian cancer.


METHODS
The material used comprised 63 surgically resected specimens obtained from female patients undergoing gynecologic surgery at Kyorin University School of Medicine (Tokyo, Japan). The expression of LAT1 in 53 cases of ovarian cancers was determined by Western blot and immunohistochemical staining, and results were compared with those of normal ovarian tissues (5 cases) and benign ovarian tumors (5 cases). Furthermore, we examined the effect of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), the classic inhibitor of system L on the survival, the migration, and the uptake of l-leucine by human epithelial ovarian cancer cell line (OVCAR-3).


RESULTS
The LAT1 was significantly up-regulated in various human epithelial ovarian cancers that was localized predominantly on their plasma membrane and in the plasma membrane of the ovarian cancer cell line in conjunction with 4F2hc via disulfide bonds. The BCH inhibited the proliferation and the migration of the OVCAR-3 cells and the uptake of [14C]l-leucine by these cells in a dose-dependent manner. The OVCAR-3 cells did not express LAT2, and the uptake of [14C]l-leucine by these cells was Na-independent and almost completely inhibited by BCH. Thus, our findings indicated that most l-leucine uptake in OVCAR-3 cells was mediated by LAT1.


CONCLUSIONS
The LAT1 plays significant roles in nutrition, proliferation, and migration of ovarian cancer. Then, LAT1 inhibition would be useful for anticancer therapy in suppressing tumor growth without affecting normal tissues.
Kaji
Masahiko
M
Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Kabir-Salmani
Maryam
M
Anzai
Naohiko
N
Jin
Chun Ji
CJ
Akimoto
Yoshihiro
Y
Horita
Ayako
A
Sakamoto
Atsuhiko
A
Kanai
Yoshikatsu
Y
Sakurai
Hiroyuki
H
Iwashita
Mitsutoshi
M
D000598:Amino Acids, Cyclic / Q000494:pharmacology; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D027283:Large Neutral Amino Acid-Transporter 1 / Q000276:immunology / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology; D014407:Tumor Cells, Cultured
D000598:Amino Acids, Cyclic; D027283:Large Neutral Amino Acid-Transporter 1; D010446:Peptide Fragments; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D007930:Leucine