| 研究実績の概要 |
Clinical significance of L-type amino acid transporter 1 (LAT1) expression was achieved in this research. Clinicopathological studies disclosed vital roles of LAT1 for the growth and prognosis in a variety of cancer including biliary tract cancer by in vitro experiment, animal studies, and clinical examination. These data suggest that LAT1 would be a molecular target of anti-cancer therapy of cancer.
Clinical significance of L-[3-18F]-α-methyl tyrosine (18F-FAMT) PET have been examined in various human cancers. 18F-FAMT is accumulated in tumor specifically via LAT1. Uptake of 18F-FAMT within tumor cells is useful for differentiating between benign lesions and malignant tumors. Additionally, the high uptake of 18F-FAMT is a promising marker for predicting poor outcome of patients. 18F-FAMT PET would be an imaging marker of LAT1-targeted therapy.
In vivo experiments revealed that LAT1 inhibitor 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) inhibited [14C] L-leucine uptake in human cholangiocarcinoma cell line named HuCCT1, and significantly decreased proliferation of HuCCT1 cells in a concentration dependent manner, and also showed significant delay in the growth of HuCCT1 xenograft in nude mice without showing significant changes in the body weight of these mice.
Moreover, other amino acid transporters have been evaluated. Possibility of prognostic potential of ASC amino-acid transporter 2 (ASCT2) have been shown in cancers originated from biliary tract.
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