Department of Neurological Surgery, Faculty of Medicine, Kagawa University, 1750-1 Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
J Neurooncol. 2010 Sep;99(2):217-25. doi: 10.1007/s11060-010-0117-9. Epub 2010 Jan 21.
L-type amino acid transporter 1 (LAT1) is a neutral amino acid transport system and is a major route for the transport of large neutral amino acids, including methionine, through the plasma membrane. LAT1 requires the heavy chain of 4F2 cell surface antigen (4F2hc) for its functional expression. Positron emission tomography (PET) with L-[methyl-(11)C] methionine (MET) provides information about amino acid metabolism in brain tumors. We conducted a clinicopathologic study to elucidate the correlation of LAT1 and 4F2hc expression with MET uptake in patients with newly diagnosed human gliomas. Thirty-three newly diagnosed glioma patients were enrolled in this study. Uptake of MET in the tumor was evaluated with the maximum standardized uptake value (SUVmax). Expression of the LAT1, 4F2hc, and CD34, and Ki-67 labeling index of the tumor were analyzed by immunohistochemical staining, and the correlation with the SUVmax in the tumors was examined. Expression of LAT1 and 4F2hc was higher in high-grade gliomas than in low-grade gliomas. The grade of LAT1 immunostaining increased with glioma grade. LAT1 was mainly expressed in the tumor cytoplasm and vascular endothelium and 4F2hc was mainly expressed in the tumor cytoplasm and plasma membrane. Expression of LAT1 but not 4F2hc was significantly correlated with MET SUVmax. Expression of LAT1 in the tumor vascular endothelium is significantly correlated with CD34 positive microvessel density. In conclusion, MET SUVmax correlates with LAT1 expression in the tumor in newly diagnosed gliomas. MET transport may be increased by an increased number of microvessels combined with a higher density or activity of LAT1 in the tumor endothelial cells in high-grade gliomas. Use of MET-PET as a molecular target combined with anti-angiogenesis in glioma therapy should be addressed in future studies.
L 型氨基酸转运蛋白 1（LAT1）是一种中性氨基酸转运系统，是包括蛋氨酸在内的大中性氨基酸通过质膜转运的主要途径。LAT1 的功能表达需要 4F2 细胞表面抗原（4F2hc）的重链。L-[甲基-（11）C]蛋氨酸（MET）的正电子发射断层扫描（PET）提供了关于脑肿瘤中氨基酸代谢的信息。我们进行了一项临床病理研究，以阐明新诊断的人类神经胶质瘤患者中 LAT1 和 4F2hc 表达与 MET 摄取的相关性。本研究纳入了 33 例新诊断的神经胶质瘤患者。通过最大标准化摄取值（SUVmax）评估肿瘤中 MET 的摄取。通过免疫组织化学染色分析肿瘤中 LAT1、4F2hc 和 CD34 的表达以及肿瘤的 Ki-67 标记指数，并检查与肿瘤中 SUVmax 的相关性。LAT1 和 4F2hc 的表达在高级别神经胶质瘤中高于低级别神经胶质瘤。LAT1 免疫染色的程度随着神经胶质瘤分级的增加而增加。LAT1 主要在肿瘤细胞质和血管内皮中表达，而 4F2hc 主要在肿瘤细胞质和质膜中表达。LAT1 的表达与 MET SUVmax 显著相关，但 4F2hc 的表达则不然。肿瘤血管内皮中 LAT1 的表达与 CD34 阳性微血管密度显著相关。总之，新诊断的神经胶质瘤中 MET SUVmax 与肿瘤中 LAT1 的表达相关。在高级别神经胶质瘤中，MET 转运可能通过肿瘤内皮细胞中微血管数量的增加以及 LAT1 密度或活性的增加而增加。在未来的研究中应探讨将 MET-PET 作为分子靶标与抗血管生成联合应用于神经胶质瘤治疗。
