Diverse roles of cell-specific hypoxia-inducible factor 1 in cancer-associated hypercoagulation.
Diverse roles of cell-specific hypoxia-inducible factor 1 in cancer-associated hypercoagulation.
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DOI：
10.1182/blood-2015-09-671982
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发表时间：
2016-03-10
期刊：
影响因子：
20.3
通讯作者：
Johnson RS
中科院分区：
文献类型：
--
作者：
Evans CE;Bendahl PO;Belting M;Branco C;Johnson RS
尽管与健康个体相比，癌症患者血栓形成的风险增加，但调节癌症诱导的高凝状态的机制尚不完全清楚。本研究的目的是使用体外凝血试验和体内癌症模型研究细胞特异性缺氧诱导因子（HIF）1α是否调节癌症相关的高凝状态。在小鼠肺和乳腺肿瘤细胞中，缺氧导致细胞粘附、凝血和纤维蛋白沉积增加;这些增加在HIF 1 α无效细胞中消除。在人乳腺肿瘤样本中，HIF 1 α水平的增加也与组织因子表达的增加相关。相反，在荷瘤小鼠中，与野生型同窝小鼠相比，内皮细胞特异性HIF 1 α（而非髓样细胞特异性HIF 1 α）的缺失使肺纤维蛋白沉积增加一倍，血栓形成增加两倍。我们的数据表明，肿瘤和内皮细胞特异性HIF 1 α可能在癌症相关凝血和血栓形成中具有相反的作用。在治疗血栓性并发症时，应仔细考虑操纵癌症患者HIF 1轴的脱靶效应。
Despite the increased risk of thrombosis in cancer patients compared with healthy individuals, mechanisms that regulate cancer-induced hypercoagulation are incompletely understood. The aim of this study was to investigate whether cell-specific hypoxia-inducible factor (HIF) 1α regulates cancer-associated hypercoagulation, using in vitro clotting assays and in vivo cancer models. In mouse lung and mammary tumor cells, hypoxia led to increases in cell adhesion, clotting, and fibrin deposition; these increases were eliminated in HIF1α null cells. Increased levels of HIF1α were also associated with increased tissue factor expression in human breast tumor samples. Conversely, deletion of endothelial (but not myeloid) cell-specific HIF1α doubled pulmonary fibrin deposition, and trebled thrombus formation compared with wildtype littermates in tumor-bearing mice. Our data suggest that tumor and endothelial cell-specific HIF1α may have opposing roles in cancer-associated coagulation and thrombosis. Off-target effects of manipulating the HIF1 axis in cancer patients should be carefully considered when managing thrombotic complications.
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影响因子：
5.3
作者：
Irokawa, M;Nishinaga, M;Shimada, K
通讯作者：
Shimada, K
影响因子：
11.2
作者：
Zerrouqi A;Pyrzynska B;Brat DJ;Van Meir EG
通讯作者：
Van Meir EG
影响因子：
64.8
作者：
Piskounova E;Agathocleous M;Murphy MM;Hu Z;Huddlestun SE;Zhao Z;Leitch AM;Johnson TM;DeBerardinis RJ;Morrison SJ
通讯作者：
Morrison SJ
DOI：
10.1161/atvbaha.108.181644
发表时间：
2010-04
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Semenza GL
通讯作者：
Semenza GL
DOI：
10.1073/pnas.1104261108
发表时间：
2011-08-09
影响因子：
11.1
作者：
Svensson, Katrin J.;Kucharzewska, Paulina;Belting, Mattias
通讯作者：
Belting, Mattias