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学科主题临床医学
pHLIP-mediated targeting of truncated tissue factor to tumor vessels causes vascular occlusion and impairs tumor growth
Li, Suping1; Tian, Yanhua2; Zhao, Ying1; Zhang, Yinlong1; Su, Shishuai1; Wang, Jing1; Wu, Meiyu1; Shi, Quanwei1; Anderson, Gregory J.3; Thomsen, Johannes4; Zhao, Ruifang1; Ji, Tianjiao1; Wang, Jie5; Nie, Guangjun1
关键词Ph Low Insertion Peptide (Phlip) Truncated Tissue Factor (Ttf) Tumor Vessel Targeting Thrombosis
刊名ONCOTARGET
2015-09-15
DOI10.18632/oncotarget.4395
6期:27页:23523-23532
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology ; Cell Biology
研究领域[WOS]Oncology ; Cell Biology
关键词[WOS]FUSION PROTEINS ; BLOOD-FLOW ; PEPTIDE ; PH ; INFARCTION ; INSERTION ; TRANSLOCATION ; MOLECULES ; RECEPTOR ; CELLS
英文摘要

Occluding tumor blood supply by delivering the extracellular domain of coagulation-inducing protein tissue factor (truncated tissue factor, tTF) to tumor vasculature has enormous potential to eliminate solid tumors. Yet few of the delivery technologies are moved into clinical practice due to their non-specific tissue biodistribution and rapid clearance by the reticuloendothelial system. Here we introduced a novel tTF delivery method by generating a fusion protein (tTF-pHLIP) consisting of tTF fused with a peptide with a low pH-induced transmembrane structure (pHLIP). This protein targets the acidic tumor vascular endothelium and effectively induces local blood coagulation. tTF-pHLIP, wherein pHLIP is cleverly designed to mimic the natural tissue factor transmembrane domain, triggered thrombogenic activity of the tTF by locating it to the endothelial cell surface, as demonstrated by coagulation assays and confocal microscopy. Systemic administration of tTF-pHLIP into tumor-bearing mice selectively induced thrombotic occlusion of tumor vessels, reducing tumor perfusion and impairing tumor growth without overt side effects. Our work introduces a promising strategy for using tTF as an anti-cancer drug, which has great potential value for clinical applications.

语种英语
WOS记录号WOS:000363157700037
项目编号2012CB934000 ; 31200752 ; 31325010 ; KGZD-EW-T06
资助机构National Basic Research Plan of China (MoST 973 Program) ; National Natural Science Foundation of China ; National Natural Science Foundation of China (National Distinguished Young Scientists program) ; Key Research Program of Chinese Academy of Sciences ; National Health and Medical Research Council of Australia ; CAS Visiting Professorship Program
引用统计
被引频次:8[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/57730
专题北京大学临床肿瘤学院_胸部肿瘤内科
作者单位1.Natl Ctr Nanosci & Technol, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China
2.Peking Univ, Acad Adv Interdisciplinary Studies, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
3.QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia
4.Univ Chinese Acad Sci, Sino Danish Ctr Educ & Res, Beijing 100190, Peoples R China
5.Peking Univ Canc Hosp & Inst, Dept Thorac Med Oncol, Beijing 100142, Peoples R China
推荐引用方式
GB/T 7714
Li, Suping,Tian, Yanhua,Zhao, Ying,et al. pHLIP-mediated targeting of truncated tissue factor to tumor vessels causes vascular occlusion and impairs tumor growth[J]. ONCOTARGET,2015,6(27):23523-23532.
APA Li, Suping.,Tian, Yanhua.,Zhao, Ying.,Zhang, Yinlong.,Su, Shishuai.,...&Nie, Guangjun.(2015).pHLIP-mediated targeting of truncated tissue factor to tumor vessels causes vascular occlusion and impairs tumor growth.ONCOTARGET,6(27),23523-23532.
MLA Li, Suping,et al."pHLIP-mediated targeting of truncated tissue factor to tumor vessels causes vascular occlusion and impairs tumor growth".ONCOTARGET 6.27(2015):23523-23532.
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