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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2005-8-12
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pubmed:abstractText |
The Semaphorins are a large family of transmembrane, GPI-anchored and secreted proteins that play an important role in neuronal and endothelial cell guidance. A human gene related to the class 6 Semaphorin family, Semaphorin 6A-1 (Sema 6A-1) was identified by homology-based genomic mining. Recent implication of Sema 3 family members in tumor angiogenesis and our expression analysis of Sema 6A-1 suggested that class 6 Semaphorin might effect tumor neovascularization. The mRNA expression of Sema 6A-1 was elevated in several renal tumor tissue samples relative to adjacent nontumor tissue samples from the same patient. Sema 6A-1 transcript was also expressed in the majority of renal clear cell carcinoma (RCC) cell lines and to a lesser extent in endothelial cells. To test the role of Sema 6A-1 in tumor angiogenesis, we engineered, expressed and purified the Sema 6A-1 soluble extracellular domain (Sema-ECD). The purified Sema-ECD was screened in a variety of endothelial cell-based assays both in vitro and in vivo. In vitro, Sema-ECD blocked VEGF-mediated endothelial cell migration. These effects were explained in part by our observation in endothelial cells that Sema-ECD inhibited VEGF-mediated Src, FAK and ERK phosphorylation. In vivo, mouse Matrigel assays demonstrated that the intraperitoneal administration of recombinant Sema-ECD inhibited both bFGF/VEGF and tumor cell line-induced neovascularization. These findings reveal a novel therapeutic utility for Sema 6A-1 (Sema-ECD) as an inhibitor of growth factor as well as tumor-induced angiogenesis.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiogenesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/Drug Combinations,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Fibroblast Growth Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Laminin,
http://linkedlifedata.com/resource/pubmed/chemical/Proteoglycans,
http://linkedlifedata.com/resource/pubmed/chemical/Ptk2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SEMA6A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Semaphorins,
http://linkedlifedata.com/resource/pubmed/chemical/VEGFA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/matrigel,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1538-4047
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pubmed:author |
pubmed-author:AlvarezEnriqueE,
pubmed-author:BoldogFerenc LFL,
pubmed-author:DhanabalMohanrajM,
pubmed-author:HackettCraigC,
pubmed-author:JeffersMikeM,
pubmed-author:KhramtsovNikolaiN,
pubmed-author:LaRochelleWilliam JWJ,
pubmed-author:LichensteinHenri SHS,
pubmed-author:MacDougallJohnJ,
pubmed-author:McQueeneyKelly DKD,
pubmed-author:ShenoySureshS,
pubmed-author:WeinerJamiJ,
pubmed-author:WuFrankF
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pubmed:issnType |
Print
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pubmed:volume |
4
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
659-68
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15917651-Adenocarcinoma, Clear Cell,
pubmed-meshheading:15917651-Angiogenesis Inhibitors,
pubmed-meshheading:15917651-Animals,
pubmed-meshheading:15917651-Carcinoma, Renal Cell,
pubmed-meshheading:15917651-Cell Movement,
pubmed-meshheading:15917651-Collagen,
pubmed-meshheading:15917651-Drug Combinations,
pubmed-meshheading:15917651-Endothelium, Vascular,
pubmed-meshheading:15917651-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:15917651-Female,
pubmed-meshheading:15917651-Fibroblast Growth Factor 2,
pubmed-meshheading:15917651-Focal Adhesion Kinase 1,
pubmed-meshheading:15917651-Humans,
pubmed-meshheading:15917651-Kidney Neoplasms,
pubmed-meshheading:15917651-Laminin,
pubmed-meshheading:15917651-Mice,
pubmed-meshheading:15917651-Mice, Nude,
pubmed-meshheading:15917651-Neovascularization, Pathologic,
pubmed-meshheading:15917651-Phosphorylation,
pubmed-meshheading:15917651-Protein Structure, Tertiary,
pubmed-meshheading:15917651-Proteoglycans,
pubmed-meshheading:15917651-RNA, Messenger,
pubmed-meshheading:15917651-Recombinant Proteins,
pubmed-meshheading:15917651-Semaphorins,
pubmed-meshheading:15917651-Vascular Endothelial Growth Factor A,
pubmed-meshheading:15917651-src-Family Kinases
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pubmed:year |
2005
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pubmed:articleTitle |
Recombinant semaphorin 6A-1 ectodomain inhibits in vivo growth factor and tumor cell line-induced angiogenesis.
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pubmed:affiliation |
CuraGen Corporation, Branford, Connecticut, USA. mdhanabal@curagen.com
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pubmed:publicationType |
Journal Article
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