Novel Glypican-3-Binding Peptide for in Vivo Hepatocellular Carcinoma Fluorescent Imaging
Novel Glypican-3-Binding Peptide for in Vivo Hepatocellular Carcinoma Fluorescent Imaging
复制标题
用于体内肝细胞癌荧光成像的新型磷脂酰肌醇蛋白聚糖 3 结合肽
DOI：
10.1021/acs.bioconjchem.6b00030
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发表时间：
2016-03-01
影响因子：
4.7
通讯作者：
Zhu, Lei
中科院分区：
文献类型：
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作者：
Zhu, Dongling;Qin, Yushuang;Zhu, Lei
磷脂酰肌醇蛋白聚糖-3（GPC 3）是磷脂酰肌醇蛋白聚糖家族的关键成员，其通过糖基-磷脂酰-肌醇（GPI）锚在细胞表面上表达。它在肝细胞癌（HCC）的发展、血管生成和转移中起重要作用。大多数HCC过表达GPC 3，而在正常成人肝脏和良性肝脏病变中可以检测到很少的GPC 3。因此，了解GPC 3在HCC肿瘤发展中的功能是重要的，因为GPC 3配体可以促进HCC的检测。本研究从噬菌体展示肽库中筛选出一个与GPC 3具有良好结合能力的12肽段，命名为TJ 12 P1，其序列为DHLASLWWGTEL。我们使用与近红外荧光（NIFR）染料Cy5.5缀合的TJ 12 P1用于肿瘤成像。静脉注射显像剂TJ 12 P1后，高GPC 3表达的肝细胞癌细胞系HepG 2的异种移植物显示出比低GPC 3表达的前列腺癌细胞系PC 3（肿瘤/肌肉比：2.03 +/- 0.23）显著更高的肿瘤蓄积（肿瘤/肌肉比：3.98 +/- 0.36）。更重要的是，使用TJ 12 P1可以可视化患者肿瘤样品中的GPC 3表达，表明该肽作为HCC检测探针的潜在用途。我们的研究已经成功地确定了一个有前途的GPC 3结合肽配体检测GPC 3在肝癌的表达不仅在体外，而且在体内的非侵入性成像。
Glypican-3 (GPC3) is a key member of the glypican family that is expressed on the cell surface by a glycosyl-phosphatidyl-inositol (GPI) anchor. It plays a significant role in hepatocellular carcinoma (HCC) development, angiogenesis, and metastasis. Most HCC overexpress GPC3, whereas little GPC3 can be detected in normal adult liver and benign liver lesions. Therefore, it is important to understand the function of GPC3 in HCC tumor development as the GPC3 ligand may facilitate detection of HCC. In this study, a 12-mer peptide with the sequence of DHLASLWWGTEL (denoted as TJ12P1) was identified by screening a phage display peptide library that demonstrated ideal GPC3 binding affinity. We used TJ12P1 conjugated with near-infrared fluorescent (NIFR) dye Cy5.5 for tumor imaging. After intravenous injection of the imaging agent, TJ12P1, xenografts of high GPC3 expressing hepatocellular carcinoma cell line, HepG2, demonstrated significantly higher tumor accumulation (tumor/muscle ratio: 3.98 +/- 0.36) than those of low GPC3 expressing prostate cancer cell line, PC3 (tumor/muscle ratio: 2.03 +/- 0.23). More importantly, GPC3 expression in tumor samples of patients could be visualized using TJ12P1, suggesting the potential use of this peptide as a probe for HCC detection. Our study has successfully identified a promising GPC3-binding peptide ligand for detecting the GPC3 expression in HCC not only in vitro but also in vivo by its noninvasive imaging.