Department of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, Japan.
Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Osaka, Japan.
Sci Rep. 2024 Nov 18;14(1):28458. doi: 10.1038/s41598-024-79425-9.
L-type amino acid transporter 1 (LAT1) is upregulated in various cancers and contributes to the growth and proliferation of cancer cells. Previous clinicopathological studies have revealed associations between the high expression of LAT1 and the poor prognosis in multiple cancer types. However, in those studies, the expression of LAT1 has been evaluated solely by immunohistochemistry on resected tumors or tissue biopsies. Cancer cell-derived exosomes are attracting increasing attention as a resource of diagnostic, prognostic, and therapeutic biomarkers. In this study, we revealed the expression of LAT1 on exosomes from pancreatic cancer T3M-4 cells by western blotting, immunoprecipitation, and immuno-transmission electron microscopy. LAT1 was generally detected by western blotting and ELISA on exosomes from several pancreatic, biliary tract, and ovarian cancer cells. Notably, similar trends existed between the abundance of exosomal LAT1 and the cellular LAT1 expression levels. The expression of LAT1 on exosomes in vivo was verified using the peritoneal wash from intraperitoneal T3M-4 tumor-bearing mice. These results indicate that exosomal LAT1 released from cancer cells holds significant potential as a novel biomarker for diagnosis and prognosis.
L 型氨基酸转运蛋白 1(LAT1)在各种癌症中上调,并有助于癌细胞的生长和增殖。先前的临床病理研究表明,LAT1 的高表达与多种癌症类型的不良预后相关。然而,在这些研究中,LAT1 的表达仅通过对切除的肿瘤或组织活检进行免疫组织化学评估。癌细胞衍生的外泌体作为诊断、预后和治疗生物标志物的资源正受到越来越多的关注。在这项研究中,我们通过 Western blot、免疫沉淀和免疫透射电子显微镜揭示了胰腺癌细胞 T3M-4 来源的外泌体上 LAT1 的表达。Western blot 和 ELISA 检测到几种胰腺、胆道和卵巢癌细胞来源的外泌体中 LAT1 的一般表达。值得注意的是,外泌体 LAT1 的丰度与细胞内 LAT1 表达水平之间存在相似的趋势。通过腹腔内 T3M-4 荷瘤小鼠的腹腔冲洗液验证了外泌体 LAT1 在体内的表达。这些结果表明,源自癌细胞的外泌体 LAT1 作为一种新型诊断和预后生物标志物具有重要潜力。