Recent Advances in Patient Treatment and Care (Track)




Properties of L-type Amino Acid Transporter 1 (LAT1) in Epidermal Ovarian Cancer

Maryam Kabir-Salmani
Department of Molecular Genetics, National Institute of Genetic Engineering and Biotechnology, Shahrak-e-Pajoohesh, Tehran-Karaj Highway, Tehran, Iran

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 metastasis of ovarian cancer.

Methods: The material used comprised 63 surgically resected specimens obtained from female patients undergoing gynecological 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 BCH, the classic inhibitor of system L on the survival, migration, and the uptake of L-leucine by human epithelial ovarian cancer cell line (OVCAR-3).

Results: LAT1 was significantly up regulated in human epithelial ovarian cancers and in the plasma membrane of ovarian cancer cell line in conjunction with 4F2hc via disulfide bonds. BCH inhibited proliferation and migration of OVCAR-3 cells and the uptake of [14C]L-leucine by these cells in a dose-dependent manner. 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 the majority of L-leucine uptake in OVCAR-3 cells was mediated by LAT1.

Conclusions: 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.