Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.
Center of Hematology and Blood & Marrow Transplantation, The First Central Hospital of Mongolia, Ulaanbaatar, 14210, Mongolia.
Sci Rep. 2021 Nov 4;11(1):21638. doi: 10.1038/s41598-021-00811-8.
L-type neutral amino acid transporter 1 (LAT1) is a heterodimeric membrane transport protein involved in neutral amino acid transport. LAT1 is highly expressed in various malignant solid tumors and plays an essential role in cell proliferation. However, its role in malignant lymphoma remains unknown. Here, we evaluated LAT1 expression level in tissues from 138 patients with Non-Hodgkin lymphoma (NHL). Overexpression of LAT1 was confirmed in all types of NHL and we found that there is a significant correlation between the level of LAT1 expression and lymphoma grade. The LAT1 expression was higher in aggressive types of lymphomas when compared with static types of lymphomas, suggesting that active tumor proliferation requires nutrient uptake via LAT1. The expression level of LAT1 was inversely correlated with patients' survival span. Furthermore, pharmacological inhibition of LAT1 by a specific inhibitor JPH203 inhibits lymphoma cell growth. In conclusion, our study demonstrated that LAT1 expression can be used as a prognostic marker for patients with NHL and targeting LAT1 by JPH203 can be a novel therapeutic modality for NHL.
L 型中性氨基酸转运蛋白 1（LAT1）是一种参与中性氨基酸转运的异二聚体膜转运蛋白。LAT1 在各种恶性实体肿瘤中高度表达，在细胞增殖中发挥重要作用。然而，其在恶性淋巴瘤中的作用尚不清楚。在这里，我们评估了 138 例非霍奇金淋巴瘤（NHL）患者组织中的 LAT1 表达水平。证实所有类型的 NHL 中均过度表达了 LAT1，并且我们发现 LAT1 表达水平与淋巴瘤分级之间存在显著相关性。与静止型淋巴瘤相比，侵袭性淋巴瘤中 LAT1 的表达更高，这表明活跃的肿瘤增殖需要通过 LAT1 摄取营养。LAT1 的表达水平与患者的生存跨度呈负相关。此外，通过特异性抑制剂 JPH203 抑制 LAT1 的表达可抑制淋巴瘤细胞的生长。总之，我们的研究表明，LAT1 的表达可以作为 NHL 患者的预后标志物，通过 JPH203 靶向 LAT1 可能成为 NHL 的一种新的治疗方法。
