Department of Molecular Imaging and Nuclear Medicine, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Mol Carcinog. 2019 Feb;58(2):247-257. doi: 10.1002/mc.22923. Epub 2018 Oct 25.
The aim of this study is to investigate the role of CD147 in glucose metabolic regulation and its association with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment sensitivity prediction using F-fluorodeoxyglucose ( F-FDG) PET/CT imaging in non-small cell lung cancer (NSCLC). In this study, four human NSCLC cell lines with different EGFR-TKI responses were used to detect p-EGFR/EGFR and CD147 expression via Western blotting and flow cytometric analyses. Radioactive uptake of F-FDG by established stable NSCLC cell lines (HCC827, H1975) with different levels of CD147 expression and the corresponding xenografts was assessed through γ-radioimmunoassays in vitro and micro-PET/CT imaging in vivo to study the role of CD147 in glucose metabolic reprogramming. Correlation analyses were performed to investigate the association between CD147 expression and PD-L1 expression in stable NSCLC cell lines. Higher CD147 expression was found in EGFR-TKI-sensitive NSCLC cell lines than in relatively resistant NSCLC cell lines (HCC827>PC9>A549>H1975). CD147 could promote F-FDG uptake by HCC827 and H1975 cells in vitro and in vivo through an EGFR-initiated Akt/mTOR-dependent signaling pathway. Programmed cell death-ligand 1 (PD-L1) expression was positively correlated with CD147 expression in human NSCLC cell lines. EGFR-TKI treatment sensitivity prediction in NSCLC using F-FDG PET/CT imaging significantly correlated with CD147-mediated glucose metabolic regulation via the Akt/mTOR-dependent pathway. Moreover, PD-L1 expression in NSCLC cell lines could be regulated by CD147, suggesting a potential immunosuppression induced by the upregulation of tumor glucose metabolism.
本研究旨在探讨 CD147 在葡萄糖代谢调节中的作用及其与表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）治疗敏感性预测的关系，方法是使用 F-氟脱氧葡萄糖（ F-FDG）正电子发射断层扫描（PET/CT）成像对非小细胞肺癌（NSCLC）进行研究。在这项研究中，使用了四种对 EGFR-TKI 反应不同的人 NSCLC 细胞系，通过 Western blot 和流式细胞术分析检测 p-EGFR/EGFR 和 CD147 的表达。通过体外γ放射性免疫分析和体内 micro-PET/CT 成像评估具有不同 CD147 表达水平的已建立稳定 NSCLC 细胞系（HCC827、H1975）及其相应的异种移植物对 F-FDG 的放射性摄取，以研究 CD147 在葡萄糖代谢重编程中的作用。进行了相关性分析，以研究稳定 NSCLC 细胞系中 CD147 表达与 PD-L1 表达之间的关联。在 EGFR-TKI 敏感的 NSCLC 细胞系中发现 CD147 表达高于相对耐药的 NSCLC 细胞系（HCC827>PC9>A549>H1975）。CD147 可以通过 EGFR 起始的 Akt/mTOR 依赖性信号通路促进 HCC827 和 H1975 细胞在体外和体内摄取 F-FDG。人 NSCLC 细胞系中程序性细胞死亡配体 1（PD-L1）的表达与 CD147 表达呈正相关。使用 F-FDG PET/CT 成像对 NSCLC 进行 EGFR-TKI 治疗敏感性预测与 Akt/mTOR 依赖性途径介导的 CD147 调节的葡萄糖代谢密切相关。此外，NSCLC 细胞系中的 PD-L1 表达可以受到 CD147 的调节，这表明肿瘤葡萄糖代谢上调可能引起潜在的免疫抑制。
