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豊田 実*; 解良 恭一*; 大島 康宏; 石岡 典子; 紫野 正人*; 坂倉 浩一*; 高安 幸弘*; 高橋 克昌*; 富永 英之*; 織内 昇*; et al.
British Journal of Cancer, 110(10), p.2506 - 2513, 2014/05
被引用回数：106 パーセンタイル：95.25(Oncology)Amino-acid transporters are necessary for the tumor cell growth and survival, and play a crucial role in the development of cancer. But, it remains unclear about the prognostic significance of L-type amino acid transporter 1 (LAT1), System ASC amino acid transporter 2 (ASCT2) and xCT expression in patients with tongue cancer. We conducted the clinicopathological study to investigate the protein expression of these amino acid transporters in tongue cancer. Eighty-five patients with surgically resected tongue cancer were evaluated. Tumor sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, CD98, Ki-67, CD34 and p53. The expression of LAT1 and ASCT2 was significantly associated with disease staging, lymph node metastasis, lymphatic permeation, vascular invasion, CD98 expression and cell proliferation (Ki-67). xCT expression indicated a significant association with advanced stage and tumor factor, correlated with CD98. By univariate analysis, both LAT1 and ASCT2 had a significant relationship with prognosis. Multivariate analysis confirmed that LAT1 were independent prognostic factors for predicting poor prognosis. These results suggest that LAT1 and ASCT2 can serve as a significant prognostic factor for predicting worse outcome after surgical treatment and may play an important role in the development and pathogenesis for tongue cancer.
解良 恭一*; 豊田 実*; 大島 康宏; 織内 昇*; 金井 好克*; 小山 徹也*; 山田 正信*; 浅尾 高行*; 近松 一朗*
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This study was conducted to determine biological significance of L-type amino acid transporter 1 (LAT1) expression and investigate whether LAT1 could be a prognostic biomarker for tongue cancer. Eighty-five patients with surgically resected tongue cancer were evaluated. Tumor sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, CD98, CD147, Ki-67, microvessel density determined by CD34, and p53. Biological significance of LAT1 expression was investigated by 
experiments with LAT inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) using tongue cell line. LAT1, ASCT2, xCT, CD98 and CD147 were highly expressed in 61%, 59%, 21%, 45% and 33%, respectively. The expression of LAT1 was significantly associated with disease staging, lymph node metastasis, lymphatic permeation, cell proliferation (Ki-67), and the expression level of CD98, ASCT2 and CD147 as amino acid transporter complexes. Multivariate analysis confirmed that LAT1 was an independent prognostic factor for predicting poor prognosis. 
preliminary experiment indicated that BCH significantly suppressed growth of the tumor and yielded an additive therapeutic efficacy to cisplatin. These rusults suggests that LAT1 can serve as a promising pathological marker to predict the outcome in patients with tongue cancer. Inhibition of LAT1 may be an effective targeted therapy for this distressing disease.
