Abstract:
:Heparanase is an endo-β-glucuronidase that enzymatically cleaves heparan sulfates (HS) and heparan sulfate proteoglycan (HSPG) structures. Heparanase expression levels by tumors were correlated with cell invasion, angiogenic activity, and poor prognosis. Heparanase can also possess pro-tumorigenic effects independent of its enzymatic activity. Using human melanoma MV3 cells, we demonstrate that latent heparanase activates in a tightly temporary-regulated manner the binding function of the integrin very late antigen-4 (VLA-4), an important component in the metastatic spread of melanoma cells. shRNA-mediated knockdown of syndecan-4 (SDC-4) indicated that this proteoglycan is the key element to convey heparanase binding via focal adhesion complex formation, detected by vinculin staining, to an upregulated VLA-4 binding function. This inside-out signaling pathway of VLA-4 involved activated FAK and Akt, but apparently not PKCα/δ. VLA-4, however, appears representative of other integrins which together impact the heparanase/integrin activation axis in tumorigenicity. Biosensor measurements provided an insight as to how heparin can interfere with this activation process. While low-molecular-weight heparin (LMWH) cannot replace heparanase bound to SDC-4, LMWH can compete with SDC-4 binding of heparanase. Since blockade of heparanase by LMWH has functional consequences for reduced VLA-4 binding, latent heparanase appears as a novel, so far unnoticed target of heparin, underlying its antimetastatic activity.
journal_name
Semin Thromb Hemostjournal_title
Seminars in thrombosis and hemostasisauthors
Gerber U,Hoß SG,Shteingauz A,Jüngel E,Jakubzig B,Ilan N,Blaheta R,Schlesinger M,Vlodavsky I,Bendas Gdoi
10.1055/s-0035-1544229subject
Has Abstractpub_date
2015-03-01 00:00:00pages
244-54issue
2eissn
0094-6176issn
1098-9064journal_volume
41pub_type
杂志文章abstract::Most plasma proteins are present in both normal and atherosclerotic intima, and their concentrations in intimal interstitial fluid are directly related to plasma concentration and molecular size. All intimal samples also contain soluble fibrin-fibrinogen-related antigens, consisting of variable mixtures of fibrinogen ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
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journal_title:Seminars in thrombosis and hemostasis
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journal_title:Seminars in thrombosis and hemostasis
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journal_title:Seminars in thrombosis and hemostasis
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journal_title:Seminars in thrombosis and hemostasis
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pub_type: 杂志文章,评审
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journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-996021
更新日期:1998-01-01 00:00:00
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journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
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journal_title:Seminars in thrombosis and hemostasis
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journal_title:Seminars in thrombosis and hemostasis
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journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0037-1604092
更新日期:2018-03-01 00:00:00
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journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0034-1370795
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journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-1002786
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journal_title:Seminars in thrombosis and hemostasis
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doi:10.1055/s-0032-1304717
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journal_title:Seminars in thrombosis and hemostasis
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doi:10.1055/s-0029-1214155
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journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0030-1267043
更新日期:2010-11-01 00:00:00
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journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0030-1255447
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journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
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journal_title:Seminars in thrombosis and hemostasis
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journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-1002708
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journal_title:Seminars in thrombosis and hemostasis
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更新日期:2017-07-01 00:00:00
abstract::Severe factor XI (FXI) deficiency is an injury-related bleeding disorder common in Ashkenazi Jews and rare worldwide. In the past two decades, more than 180 mutations in the FXI gene have been reported in patients with FXI deficiency, five of which show a founder effect (Cys38Arg, Gln88Stop, Cys128Stop, Glu117stop, an...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0029-1225764
更新日期:2009-06-01 00:00:00
abstract::Severe trauma is the leading cause of death globally. Though improved resuscitation, particularly early initiation, has reduced the 24-hour mortality rate, the overall morbidity and 30-day mortality remain high mostly due to massive hemorrhage and head injury in the early stages and sepsis and multiorgan failure later...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
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更新日期:2020-03-01 00:00:00
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journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2005-869522
更新日期:2005-04-01 00:00:00
abstract::We experienced 23 cases of venous thrombosis after gynecological surgery for the past 12 years at Tokyo Women's Medical University Hospital, representing 0.345 % of all patients. Eighteen of the 23 cases had deep venous thrombosis (DVT) including five cases followed by pulmonary embolism (PE), and five cases had PE wi...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-996036
更新日期:1998-01-01 00:00:00
abstract::In this short review I have tried to report the literature findings and describe some of our observations on fibrinolysis and atherosclerosis. Although at this time it is difficult to state that diminished FA plays a pathogenic role in atherosclerosis, it certainly seems to represent a risk factor. ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-1003541
更新日期:1986-04-01 00:00:00
abstract::In order to assess inhibitor development in previously untreated patients (PUPs) with severe (factor VIII [FVIII]<1%) and moderate (FVIII 1 to 5%) hemophilia A, a prospective study was initiated in 1976. During the 23-year study period, 72 hemophiliacs were frequently exposed prophylactically or on demand to plasma-de...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2002-32664
更新日期:2002-06-01 00:00:00
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journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2001-14075
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abstract::The purpose of this article is to review the use of blood products and hemostatic agents in the management of coagulopathy at the time of postpartum hemorrhage. Blood product administration strategies are broadly reviewed, including the role of the blood bank, the role of massive transfusion protocols, the role of lab...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0036-1593417
更新日期:2016-10-01 00:00:00
abstract::Type 2B von Willebrand disease (VWD2B) is a rare, autosomal-dominant inherited bleeding disorder, characterized by an enhanced ristocetin-induced platelet aggregation in platelet-rich plasma and often with variable degree of thrombocytopenia and loss of high-molecular-weight multimers von Willebrand factor (VWF). All ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0036-1579638
更新日期:2016-07-01 00:00:00