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	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
刊名	Oncotarget
	2015-09-15
卷号	6期号:27页码:23523-23532
关键词	Ph low insertion peptide (phlip) Truncated tissue factor (ttf) Tumor vessel targeting Thrombosis
ISSN号	1949-2553
通讯作者	Nie, guangjun(niegj@nanoctr.cn)
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.
WOS关键词	FUSION PROTEINS ; BLOOD-FLOW ; PEPTIDE ; PH ; INFARCTION ; INSERTION ; TRANSLOCATION ; MOLECULES ; RECEPTOR ; CELLS
WOS研究方向	Oncology ; Cell Biology
WOS类目	Oncology ; Cell Biology
语种	英语
出版者	IMPACT JOURNALS LLC
WOS记录号	WOS:000363157700037
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2176475
专题	高能物理研究所
通讯作者	Nie, Guangjun
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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