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学科主题: 临床医学
题名:
pHLIP-mediated targeting of truncated tissue factor to tumor vessels causes vascular occlusion and impairs tumor growth
作者: 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
发表日期: 2015-09-15
DOI: 10.18632/oncotarget.4395
卷: 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
所属项目编号: 2012CB934000 ; 31200752 ; 31325010 ; KGZD-EW-T06
项目资助者: 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
WOS记录号: WOS:000363157700037
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57730
Appears in Collections:北京大学临床肿瘤学院_胸部肿瘤内科_期刊论文

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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

Recommended Citation:
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.
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