Possibility of system L amino acid transporter 1 (LAT1) as a novel therapeutic target for biliary tract cancer

胆管癌における新規治療標的としてのLAT1の可能性についての検討

大島 康宏; 富永 英之*; 永森 收志*; 金井 好克*; 織内 昇*; 石岡 典子

Ohshima, Yasuhiro; Tominaga, Hideyuki*; Nagamori, Shushi*; Kanai, Yoshikatsu*; Oriuchi, Noboru*; Ishioka, Noriko

The expression of system L amino acid transporter 1 (LAT1) has been described to play essential roles in tumor growth and survival. In this study, we investigated whether LAT1 could be a novel therapeutic target for biliary tract cancer. Both expression of LAT1 and CD98 was found, and the expression of LAT1 was extremely higher than other subtypes of LAT in a biliary tract cancer cell line, HuCCT1. The uptake of [C]L-leucine was strongly inhibited by the treatment of BCH, an selective inhibitor of LAT1 and LAT2. These results indicate that the contribution of LAT1 to the uptake of amino acids was higher than other subtypes of LAT, and BCH could suppress the uptake of amino acids through LAT1 relatively. BCH decreased numbers of viable cells in a concentration-dependent manner . Furthermore, daily injection of BCH to HuCCT1-bearing mice showed significant delay of tumor growth with no change of body-weight. These results suggest that LAT1 inhibition could suppress growth of biliary tract cancer. Inhibition of LAT1 would be an effective target for the therapy of this distressing disease.