Phlip-mediated targeting of truncated tissue factor to tumor vessels causes vascular occlusion and impairs tumor growth
文献类型:期刊论文
作者 | 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
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出版日期 | 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 |
WOS记录号 | WOS:000363157700037 |
出版者 | IMPACT JOURNALS LLC |
URI标识 | http://www.irgrid.ac.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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来源:高能物理研究所
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