Construction of novel procoagulant protein targeting neuropilin-1 on tumour vasculature for tumour embolization therapy
Construction of novel procoagulant protein targeting neuropilin-1 on tumour vasculature for tumour embolization therapy
复制标题
构建针对肿瘤血管系统的 Neuropilin-1 的新型促凝血蛋白用于肿瘤栓塞治疗
DOI：
10.1080/1061186x.2019.1566337
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发表时间：
2019-01
影响因子：
4.5
通讯作者：
Yan Jianghua
中科院分区：
文献类型：
--
作者：
Zou Mingyuan;Samiullah Malik;Xu Peilan;Wang Shengyu;He Jie;Wu Ting;Luo Fanghong;Yan Jianghua
细胞跨膜受体Neuropilin-1（NRP-1）在肿瘤组织和肿瘤血管内皮细胞中过表达，而在正常组织中表达有限。本研究旨在设计一种由截断组织因子（tTF）和NRP-1靶向肽EG3287组成的新型重组蛋白tTF-EG3287。促凝蛋白一旦结合到肿瘤血管的细胞表面，通过靶向肽EG3287选择性地激活肿瘤血管中的血液凝固。本研究采用光谱酶FXa法评价重组蛋白tTF-EG3287的促凝活性。荧光共聚焦显微镜和流式细胞术分析NRP-1的靶向能力。活体成像系统用于评估重组蛋白tTF-EG3287在体内的肿瘤靶向能力。肿瘤生长抑制剂对HepG2荷瘤裸鼠具有有效的抗肿瘤活性。组织学研究显示肿瘤血管血栓形成、血栓栓塞明显，肿瘤组织细胞坏死，未见其他器官血栓形成等明显副作用。
Abstract The cellular transmembrane receptor Neuropilin-1(NRP-1) is overexpressed in tumour tissue and endothelial cells of tumour vessels, whereas it has limited expression in normal tissues. This study aimed to design a novel recombinant protein tTF-EG3287, which consisting of the truncated tissue factor (tTF) and the NRP-1 targeting peptide EG3287. The procoagulant protein selectively activates blood coagulation in tumour vessels once bound to the cell surface of the tumour vasculature by a targeting peptide EG3287. In this study, procoagulant activity of the recombinant protein tTF-EG3287 was evaluated by Spectozyme FXa assay. NRP-1 targeting ability was analysed by fluorescence confocal microscopy and flow cytometry. The living imaging system was used to assess the tumour targeting ability of recombinant proteins tTF-EG3287 in vivo. Tumour growth inhibition showed effective antitumor activity in HepG2 tumour-bearing nude mice. Histological study showed obvious thrombosis and thromboembolism in tumour vessels and cell necrosis of tumour tissue, without any clear side effect such as thrombosis in other organs.
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影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
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