Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
Thorac Cancer. 2020 May;11(5):1245-1257. doi: 10.1111/1759-7714.13383. Epub 2020 Mar 11.
Lung adenocarcinoma (LUAD) is one of the most deadly thoracic tumors. Reprogrammed glycolytic metabolism is a hallmark of cancer cells and significantly affects several cellular functions. In the current study, we aimed to investigate cluster of differentiation 147 (CD147)-mediated glucose metabolic regulation in LUAD and its association with F-FDG PET/CT imaging.
The expression profile and prognostic potential of CD147 in LUAD were analyzed using UALCAN and a Kaplan-Meier plotter. Tissue immunohistochemical analyses and PET metabolic parameters were used to identify the relationship between CD147 expression and reprogrammed glycolysis. The role of CD147 in glucose metabolic reprogramming was assessed by radioactive uptake of F-FDG through γ-radioimmunoassays in vitro and micro-PET/CT imaging in vivo. Western blotting assays were used to determine the expression level of monocarboxylate transporter 1 (MCT1) and MCT4 in established human LUAD cell lines (ie, HCC827 and H1975) with different CD147 expression levels via lentiviral transduction.
CD147 was highly expressed in LUAD. A significant positive correlation existed between CD147 expression and PET metabolic parameters(SUVmax,SUVmean, SUVpeak). CD147 could promote radioactive uptake of F-FDG in vitro and in vivo, suggesting the ability of CD147 to enhance glycolytic metabolism. Furthermore, as an obligate chaperone for MCT1 and MCT4, CD147 positively correlated with MCT1 and MCT4 expression in LUAD tissues and established cell lines with different CD147 expression.
Our study revealed that CD147 is a promising novel target for LUAD treatment and CD147-mediated glucose metabolism demonstrated its contribution to the predictive role of F-FDG PET/CT imaging for targeted therapeutic efficacy.
肺腺癌（LUAD）是最致命的胸部肿瘤之一。重新编程的糖酵解代谢是癌细胞的一个标志，显著影响多种细胞功能。在本研究中，我们旨在研究 CD147 介导的葡萄糖代谢调节在 LUAD 中的作用及其与 F-FDG PET/CT 成像的关联。
使用 UALCAN 和 Kaplan-Meier 绘图器分析 LUAD 中 CD147 的表达谱和预后潜力。组织免疫组织化学分析和 PET 代谢参数用于鉴定 CD147 表达与重编程糖酵解之间的关系。通过体外放射性摄取 F-FDG 的γ-放射免疫测定和体内 micro-PET/CT 成像评估 CD147 在葡萄糖代谢重编程中的作用。通过慢病毒转导在具有不同 CD147 表达水平的已建立的人 LUAD 细胞系（即 HCC827 和 H1975）中，通过 Western blot 分析确定单羧酸转运蛋白 1（MCT1）和 MCT4 的表达水平。
CD147 在 LUAD 中高表达。CD147 表达与 PET 代谢参数（SUVmax、SUVmean、SUVpeak）之间存在显著正相关。CD147 可以促进体外和体内 F-FDG 的放射性摄取，表明 CD147 增强糖酵解代谢的能力。此外，作为 MCT1 和 MCT4 的必需伴侣蛋白，CD147 与 LUAD 组织和不同 CD147 表达的建立细胞系中的 MCT1 和 MCT4 表达呈正相关。
我们的研究表明，CD147 是 LUAD 治疗的有前途的新靶点，CD147 介导的葡萄糖代谢证明了其对 F-FDG PET/CT 成像预测靶向治疗效果的贡献。
