Hashimoto Nao, Nakajima Kei, Akashi Yoshihiko, Kokubun Katsutoshi, Sugahara Keisuke, Katakura Akira, Matsuzaka Kenichi
Department of Oral Pathobiological Science and Surgery, Tokyo Dental College, Tokyo, Japan.
Department of Pathology, Tokyo Dental College, Tokyo, Japan.
Sci Rep. 2025 Aug 29;15(1):31927. doi: 10.1038/s41598-025-17702-x.
Studies have indicated moderate to high choline transporter-like protein 1 (CTL1) expression in colon, pancreatic, breast, lung, and glioma cancers. However, studies on CTL1 in oral squamous cell carcinoma (OSCC), a highly invasive cancer, remain limited. We aimed to investigate the expression and localization of CTL1 in OSCC and its association with cell proliferation. Using in vitro experiments, we evaluated CTL1 expression and localization in the OSCC cell lines HSC-3 and HSC-4 by immunocytochemistry and western blotting. A cell proliferation assay was performed using hemicolinium-3, a choline uptake inhibitor. Using in vivo and ex vivo experiments, we assessed CTL1 expression in rat and human tongue cancer tissues by immunohistochemical and immunofluorescent staining. Here, we show that CTL1 is strongly expressed intracellularly and localized in organelles of HSC-3 and HSC-4 cells. CTL1 significantly accumulated around the nucleus in Ki67-positive cells with proliferative potential, suggesting increased production and transport of CTL1. Conversely, the number of cells in the HC-3 treated group in both HSC-3 and HSC-4 cells decreased. These results suggest that intracellular production of CTL1 is further increased in Ki67-positive cells, and choline uptake may lead to cell proliferation. In vivo and ex vivo experiments revealed high CTL1 expression in tongue cancer, with stronger expression in well-differentiated tumors than that in poorly-differentiated ones. Our study demonstrates that CTL1 is associated with OSCC proliferation and tumor differentiation. These findings suggest that CTL1 may function as a potential marker for tumor differentiation and progression of OSCC.
研究表明，胆碱转运体样蛋白1（CTL1）在结肠癌、胰腺癌、乳腺癌、肺癌和神经胶质瘤中呈中度至高表达。然而，对于高侵袭性癌症——口腔鳞状细胞癌（OSCC）中CTL1的研究仍然有限。我们旨在研究CTL1在OSCC中的表达、定位及其与细胞增殖的关系。通过体外实验，我们采用免疫细胞化学和蛋白质印迹法评估了CTL1在OSCC细胞系HSC-3和HSC-4中的表达和定位。使用胆碱摄取抑制剂半胱氨酸-3进行细胞增殖试验。通过体内和体外实验，我们采用免疫组织化学和免疫荧光染色评估了大鼠和人舌癌组织中CTL1的表达。在此，我们表明CTL1在细胞内强烈表达，并定位于HSC-3和HSC-4细胞的细胞器中。CTL1在具有增殖潜力的Ki67阳性细胞的细胞核周围显著积聚，表明CTL1的产生和转运增加。相反，HSC-3和HSC-4细胞中HC-3处理组的细胞数量减少。这些结果表明，Ki67阳性细胞中CTL1的细胞内产生进一步增加，胆碱摄取可能导致细胞增殖。体内和体外实验显示舌癌中CTL1高表达，高分化肿瘤中的表达强于低分化肿瘤。我们的研究表明，CTL1与OSCC的增殖和肿瘤分化相关。这些发现表明，CTL1可能作为OSCC肿瘤分化和进展的潜在标志物。
