Abstract:
INTRODUCTION:Tissue Factor Pathway Inhibitor-2 (TFPI-2) is a Kunitz-type serine proteinase inhibitor whose expression is up-regulated by VEGF in microvascular and umbilical vein endothelial cells (EC). Despite this, TFPI-2 has been suggested as anti-angiogenic molecule, due to its ability to inhibit the migration/proliferation of EC induced by VEGF. Nothing is known about the precise mechanism of TFPI-2 function tuning in tumor endothelium. AIM:Aim of this study was to investigate the role of TFPI-2 in tumor vasculature, where angiogenesis and vascular remodeling are fundamental for cancer progression. MATERIALS AND METHODS:Tumor-EC were isolated from ovarian carcinomas and cultured in vitro in presence of factors reproducing the tumor microenvironment (VEGF, FGF-2, EGF). TFPI-2 and PRSS3 silencing was achieved by small interfering RNA (siRNA). Tumor-EC migration was assayed by the wound healing assay. Transcript expression was examined by qRT-PCR. Proteolytic reactions were monitored by western blot. RESULTS:We show that tumor-EC express TFPI-2, the majority of which is released and found anchored in the extracellular matrix. Silencing the expression of TFPI-2 enhances tumor-EC migration, confirming TFPI-2 as an anti-angiogenic molecule. We had previously shown that the cancer vasculature express PRSS3, a trypsin family member able to cleave proteins containing the kunitz-type domains; we reasoned that it could potentially inhibit TFPI-2. Herein, we demonstrate in a cell free system that TFPI-2 directly interacts with and is degraded by active PRSS3. In a more complex biological context, active PRSS3 is able to remove TFPI-2 from the extracellular matrix put down by tumor-EC. Accordingly, silencing PRSS3 causes the extracellular accumulation of TFPI-2 that results in the inhibition of tumor-EC migration. CONCLUSIONS:Our results demonstrate for the first time that TFPI-2 is a direct substrate of PRSS3, which hydrolyses TFPI-2 (most likely at the Kunitz-type domains) blocking its anti migratory capability. The proteolytic inactivation of TFPI-2 by PRSS3 might represent a mechanism favoring cancer by increasing angiogenesis and vascular remodeling. ACKNOWLEDGEMENT:Supported by the Italian Association for Cancer Research (AIRC).
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Ghilardi C,Anastasia A,Avigni R,Lupi M,Giavazzi R,Bani MRdoi
10.1016/S0049-3848(16)30177-3subject
Has Abstractpub_date
2016-04-01 00:00:00pages
S192-3eissn
0049-3848issn
1879-2472pii
S0049-3848(16)30177-3journal_volume
140 Suppl 1pub_type
杂志文章abstract:BACKGROUND:There is a need to identify and develop novel thrombolytic agents that can directly digest fibrin clots from various biological resources. OBJECTIVE:To clone, express, purify, and characterize a recombinant protease named rvFMP capable of cleaving fibrinogen, fibrin polymer, and cross-linked fibrin in human...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2020.04.040
更新日期:2020-07-01 00:00:00
abstract:INTRODUCTION:Incidence and risk factors of venous thromboembolism (VTE) are well established in surgical and medical settings, but data in psychiatric units are lacking. The aim of this study was to estimate the incidence of VTE in hospitalized psychiatric patients, and to assess the risk factors for VTE in this specif...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2012.10.002
更新日期:2012-12-01 00:00:00
abstract::Murine monoclonal antibodies (mAb) were raised to a purified product of bovine PF-4, a 9,500 dalton protein with heparin neutralization activity comparable to that of human PF-4. Using a non-radioactive slide immunoenzymatic assay, four major classes of mAb could be identified when comparisons were made between purifi...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(86)90384-1
更新日期:1986-03-15 00:00:00
abstract:BACKGROUND:Few studies investigated the relationship between fibrinolysis abnormalities and residual pulmonary perfusion defects after acute pulmonary embolism (PE). OBJECTIVE:To assess the fibrinolytic profile in patients with prior PE in relation to the extent of scintigraphically detectable residual perfusion abnor...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.07.013
更新日期:2014-09-01 00:00:00
abstract::Nineteen patients, (2 adults, 17 children) with inherited bleeding disorders were infused with n-heptane-suspended-heated clotting factor concentrates. Twelve of the nineteen were previously untreated. Six patients were infused with Profilnine Heat-Treated and 13 with Profilate Heat-Treated. Five separate centers part...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(87)90074-0
更新日期:1987-06-15 00:00:00
abstract:AIMS:acutely ill medical patients are at increased risk of venous thromboembolism (VTE) and often require thromboprophylaxis, but patient selection and adequate therapeutic decisions may be difficult due to the heterogeneity and the complexity of this population. We conducted a survey among a large cohort of Italian ph...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.06.013
更新日期:2014-09-01 00:00:00
abstract::There is a close interrelation between cancer and haemostasis, which is characterized by changes in the haemostatic system, mostly an activation of coagulation in cancer patients. Venous thromboembolism (VTE) is a frequent complication of cancer and in particular of anticancer therapy and is associated with significan...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/S0049-3848(10)70005-0
更新日期:2010-04-01 00:00:00
abstract:OBJECTIVES:In this randomized management study, we examined the safety of withholding anticoagulation on the basis of negative impedance plethysmography (IPG) compared to negative contrast venography (CV) in symptomatic patients with a first episode of clinically suspected deep vein thrombosis (DVT), and we determined ...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0049-3848(01)00222-5
更新日期:2001-04-01 00:00:00
abstract:INTRODUCTION:Circulating microparticles support thrombin generation. The aim of this study is to determine the indirect microparticle activity and the parameters of thrombin generation in healthy infants. MATERIALS AND METHODS:A total of 85 infants who were brought to follow-up visits were taken into the study. Blood ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2013.11.011
更新日期:2014-02-01 00:00:00
abstract::Platelets occupy a central role at the interface between thrombosis and inflammation. At sites of vascular damage, adherent platelets physically and functionally interact with circulating leukocytes. Activated platelets release soluble factors into circulation that may have local and systemic effects on blood and vasc...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2010.10.010
更新日期:2011-03-01 00:00:00
abstract:INTRODUCTION:Thrombin or tryptase cleavage of protease-activated receptors (PAR) on human coronary artery endothelial cells (HCAEC) results in activation of a membrane-associated, calcium-independent phospholipase A2 (iPLA2) that selectively hydrolyzes plasmalogen phospholipids. Atherosclerotic plaque rupture results i...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2006.11.007
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:Although the general improvement caused by recombinant human erythropoietin (rHuEPO) in the correction of uraemic anaemia cannot be questioned, some data suggest that the changes in the haemostasis, endothelial function and oxidative stress (SOX) are induced. The aim of the present study was to investigate...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章
doi:10.1016/j.thromres.2007.02.004
更新日期:2007-01-01 00:00:00
abstract::Chloroquine inhibited aggregation of rat blood platelets in a dose-dependent way. The inhibitory effect decreased, depending on the aggregation stimulus used, in the rank order of potency: ADP > thrombin > A23187. Effect of 1 millimolar chloroquine on A23187-stimulated aggregation was significantly decreased or comple...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(94)90270-4
更新日期:1994-06-01 00:00:00
abstract:INTRODUCTION:Warfarin is the most widely used oral anticoagulant. It has been suggested that anticoagulation effect of warfarin is significantly associated with the polymorphism of certain genes, including Cytochrome P450 complex subunit 2C9 (CYP2C9), Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1), Gamma-Glutam...
journal_title:Thrombosis research
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.thromres.2009.10.017
更新日期:2010-04-01 00:00:00
abstract:BACKGROUND:Clopidogrel, cilostazol, and aspirin were compared in terms of efficacy and safety for primary prevention of stroke in peripheral artery disease (PAD) patients. METHODS:This retrospective cohort study analyzed data contained in the Taiwan National Health Insurance Bureau database for patients treated for PA...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2013.01.036
更新日期:2013-08-01 00:00:00
abstract::There are some issues in the current factor (F)VIII replacement therapy for severe hemophilia A. One is mental and physical burden for the multiple intravenous infusions, and the other is difficulty in the hemostatic treatment for the patients with FVIII inhibitor. The development of novel drug with fully hemostatic e...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/S0049-3848(16)30361-9
更新日期:2016-05-01 00:00:00
abstract::We have previously reported on a microassay based on human kininogens as cysteine proteinase inhibitors (CPIs), which could quantify partially purified kininogens from different biological fluids (J Pharmacol Meth 26, 113-124, 1991). In the present study we describe a functional method that, when assuming a 1:1 stoich...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(96)00073-4
更新日期:1996-05-01 00:00:00
abstract::Two monoclonal antibodies against plasminogen and two against alpha-2-antiplasmin were characterized regarding their binding properties towards their respective native and modified antigens and towards the plasmin-alpha-2-antiplasmin complex. Using an ELISA system, the two monoclonal antibodies against plasminogen (MP...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(87)90311-2
更新日期:1987-03-01 00:00:00
abstract::The in vitro and in vivo pharmacological properties of two oversulfated dermatan sulfate (DS) derivatives, S-DS1 and S-DS2, containing 2 and 3.7 sulfate groups/disaccharide unit respectively were compared to those of the parent DS (1 sulfate group/disaccharide unit). In a purified system the ability of S-DS1 and of S-...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(88)90094-1
更新日期:1988-10-15 00:00:00
abstract:INTRODUCTION:Venous thromboembolism (VTE) is a frequent clinical event in patients with gynecologic cancer. However, studies that exclusively address the incidence of VTE according the type of gynecologic cancer are poorly reported. OBJECTIVE:To analyze the incidence of VTE and the associated factors in women with dif...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2019.11.009
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Rate of thalidomide-related VTE and risk factors in Japanese myeloma patients are not clear and effects of thromboprophylaxis remain controvertial. PATIENTS AND METHODS:We retrospectively analyzed a cohort data of registered Japanese myeloma patients treated with thalidomide-based regimens between 2009 and ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2012.11.014
更新日期:2013-02-01 00:00:00
abstract:BACKGROUND:The level of platelet reactivity (PR) inhibition obtained after P2Y12-ADP receptor antagonist loading dose (LD) is associated with the ischemic and bleeding risk following percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS). OBJECTIVE:We aimed to evaluate the level of PR inhibition ac...
journal_title:Thrombosis research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.thromres.2013.04.030
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND:Multiple sclerosis (MS) often causes progressive loss of mobility, leading to limb paralysis. Venous and lymphatic stasis is a risk condition for venous thromboembolism (VTE). There is, however, no data on the frequency of VTE complicating the progression of MS. The aim of this study was to assess the freque...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2009.06.023
更新日期:2010-04-01 00:00:00
abstract:INTRODUCTION:To determine whether the HIT IgG class platelet factor 4 (PF4) enzyme immunoabsorbant assay (EIA) influenced the duration of parenteral direct thrombin inhibitor (pDTI) therapy or bleeding risk in patients started on pDTI for a presumed diagnosis of HIT. MATERIALS/METHODS:187 patients started on pDTI for ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.04.030
更新日期:2014-07-01 00:00:00
abstract:INTRODUCTION:Remote ischaemic conditioning (RIC) has been shown to prevent platelet activation during ablation for atrial fibrillation. RIC has also been associated with more postoperative transfusion in the off-pump coronary artery bypass graft surgery (OPCAB) patients. We evaluated the effects of RIC on coagulation f...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2020.01.004
更新日期:2020-03-01 00:00:00
abstract::Hemorrhagic and thrombotic complications are common in the term and preterm infant. Limited information is currently available about neonatal platelet structure and function, and how these may predispose infants to bleeding problems. This study comparing platelet ultrastructure of 71 different term and preterm infants...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(94)90039-6
更新日期:1994-03-15 00:00:00
abstract::Two isozymes of a native form of human plasminogen (plg), Glu-plg I and II, were isolated. Glu-plg I or II was activated by urokinase (UK) or streptokinase (SK) in the presence of fibrinogen or fibrin. The activation of Glu-plg I was enhanced more than that of Glu-plg II in the presence of fibrin. Fibrin caused better...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(85)90224-5
更新日期:1985-08-01 00:00:00
abstract::Fibrin is found in most solid tumours, and there is speculation regarding its role in tumour invasion and metastasis. An assay to quantitate fibrin levels in tissues would be a useful preliminary tool in assessing the above. Such an assay to quantitatively detect levels of fibrin in various types of canine tumour was ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(99)00054-7
更新日期:1999-10-01 00:00:00
abstract:BACKGROUND:Abdominal obesity has been found to be associated with an increased risk of deep vein thrombosis (DVT). Whether patients with abdominal obesity have an increased risk of recurrence is currently unknown. METHODS:Patients with objective diagnosis of DVT and a life expectancy of greater than 6 months underwent...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2006.05.013
更新日期:2007-01-01 00:00:00
abstract::Chronic thromboembolic pulmonary hypertension (CTEPH) is the most severe long term complication of acute pulmonary embolism (PE). Untreated, CTEPH is associated with a very poor prognosis and high risk of mortality, although curation can be achieved by surgical removal of the obstructive endothelialised thromboemboli ...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2016.12.026
更新日期:2017-03-01 00:00:00