Source:http://linkedlifedata.com/resource/pubmed/id/14739228
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
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| pubmed:dateCreated |
2004-4-20
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| pubmed:abstractText |
Tissue factor pathway inhibitor (TFPI) is the major physiologic inhibitor of the extrinsic coagulation pathway. We have previously shown that TFPI is also a potent inhibitor of endothelial proliferation in vitro and of primary and metastatic tumor growth in vivo. Surprisingly, the antitumor activity of TFPI was demonstrated to be independent of its anticoagulant activity, suggesting a possible nonhemostatic mechanism of action for TFPI in these models. This antitumor mechanism may involve the very low density lipoprotein (VLDL) receptor because the in vitro antiproliferative activity of TFPI is mediated through interaction with the VLDL receptor. In the current study, we identify a 23-amino acid fragment of TFPI (TFPIc23) localized to the C-terminus, which mediates binding to the VLDL receptor. The TFPIc23 peptide inhibits endothelial cell proliferation through an apoptotic mechanism and blocks vessel outgrowth in the in vitro assays, and this activity is mediated through interaction with the VLDL receptor. In vivo, this peptide potently inhibits angiogenesis in Matrigel and chick chorioallantoic membrane models and also inhibits metastatic tumor growth. Our data demonstrate that this VLDL receptor-binding fragment of the TFPI molecule has apoptotic, antiangiogenic, and antitumor activity and suggests a possible mechanism whereby TFPI can regulate angiogenesis and tumor growth independently of its anticoagulant activity.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiogenesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/VLDL receptor,
http://linkedlifedata.com/resource/pubmed/chemical/lipoprotein-associated coagulation...
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
0006-4971
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| pubmed:author |
pubmed-author:HammersHans JHJ,
pubmed-author:HembroughTodd ATA,
pubmed-author:PlumStacy MSM,
pubmed-author:PribludaVictor SVS,
pubmed-author:RuizJose FJF,
pubmed-author:StricklandDudley KDK,
pubmed-author:SwartzGlenn MGM,
pubmed-author:SwerdlowBonnie MBM,
pubmed-author:WilliamsMark SMS,
pubmed-author:ZhangLiL
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| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
103
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
3374-80
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| pubmed:dateRevised |
2004-11-17
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| pubmed:meshHeading |
pubmed-meshheading:14739228-Angiogenesis Inhibitors,
pubmed-meshheading:14739228-Animals,
pubmed-meshheading:14739228-Antineoplastic Agents,
pubmed-meshheading:14739228-Apoptosis,
pubmed-meshheading:14739228-Binding Sites,
pubmed-meshheading:14739228-Carcinoma, Lewis Lung,
pubmed-meshheading:14739228-Cell Division,
pubmed-meshheading:14739228-Chick Embryo,
pubmed-meshheading:14739228-Endothelium, Vascular,
pubmed-meshheading:14739228-Humans,
pubmed-meshheading:14739228-Lipoproteins,
pubmed-meshheading:14739228-Mice,
pubmed-meshheading:14739228-Mice, Inbred C57BL,
pubmed-meshheading:14739228-Neoplasm Metastasis,
pubmed-meshheading:14739228-Neovascularization, Physiologic,
pubmed-meshheading:14739228-Peptide Fragments,
pubmed-meshheading:14739228-Receptors, LDL,
pubmed-meshheading:14739228-Umbilical Veins
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| pubmed:year |
2004
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| pubmed:articleTitle |
Identification and characterization of a very low density lipoprotein receptor-binding peptide from tissue factor pathway inhibitor that has antitumor and antiangiogenic activity.
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| pubmed:affiliation |
EntreMed, Inc, 9640 Medical Center Dr, Rockville, MD 20850,USA. toddh@entremed.com
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| pubmed:publicationType |
Journal Article
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