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Properties of L-Type Amino Acid Transporter 1 in Epidermal Ovarian Cancer
  1. Masahiko Kaji, PhD*,
  2. Maryam Kabir-Salmani, PhD,,
  3. Naohiko Anzai, PhD§,
  4. Chun Ji Jin, MD§,
  5. Yoshihiro Akimoto, PhD,
  6. Ayako Horita, PhD,
  7. Atsuhiko Sakamoto, PhD,
  8. Yoshikatsu Kanai, PhD§,
  9. Hiroyuki Sakurai, PhD§ and
  10. Mitsutoshi Iwashita, PhD*
  1. *Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan;
  2. Department of Molecular Genetics, National Institute of Genetic Engineering and Biotechnology;
  3. Cellular and Molecular Research Center, Faculty of Medicine, Shahid Beheshti Medical University, Tehran, Iran; and Departments of
  4. §Pharmacology and Toxicology,
  5. Anatomy, and
  6. Pathology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
  1. Address correspondence and reprint requests to Maryam Kabir-Salmani, PhD, Department of Molecular Genetics, National Institute of Genetic Engineering and Biotechnology, PO Box 14965-161, Shahrak-e-Pajoohesh, Tehran-Karaj Hwy, Tehran, Iran. E-mail: maryam{at}nigeb.ac.ir; and Mitsutoshi Iwashita, PhD, Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan. E-mail: iwashita{at}ks.kyorin-u.ac.jp.

Abstract

Hypothesis: 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.

  • LAT1
  • Epithelial ovarian cancer
  • BCH
  • System L
  • Amino acid transporter

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Footnotes

  • This project has been funded in part with a grant from the National Institute of Genetic Engineering and Biotechnology, Tehran, Iran, under project No. 360.

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