| http://purl.uniprot.org/citations/18594512 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18594512 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18594512 | http://www.w3.org/2000/01/rdf-schema#comment | "Angiogenesis, the growth of new blood vessels from pre-existing vasculature, is a key process in several pathological conditions, including tumour growth and age-related macular degeneration. Vascular endothelial growth factors (VEGFs) stimulate angiogenesis and lymphangiogenesis by activating VEGF receptor (VEGFR) tyrosine kinases in endothelial cells. VEGFR-3 (also known as FLT-4) is present in all endothelia during development, and in the adult it becomes restricted to the lymphatic endothelium. However, VEGFR-3 is upregulated in the microvasculature of tumours and wounds. Here we demonstrate that VEGFR-3 is highly expressed in angiogenic sprouts, and genetic targeting of VEGFR-3 or blocking of VEGFR-3 signalling with monoclonal antibodies results in decreased sprouting, vascular density, vessel branching and endothelial cell proliferation in mouse angiogenesis models. Stimulation of VEGFR-3 augmented VEGF-induced angiogenesis and sustained angiogenesis even in the presence of VEGFR-2 (also known as KDR or FLK-1) inhibitors, whereas antibodies against VEGFR-3 and VEGFR-2 in combination resulted in additive inhibition of angiogenesis and tumour growth. Furthermore, genetic or pharmacological disruption of the Notch signalling pathway led to widespread endothelial VEGFR-3 expression and excessive sprouting, which was inhibited by blocking VEGFR-3 signals. Our results implicate VEGFR-3 as a regulator of vascular network formation. Targeting VEGFR-3 may provide additional efficacy for anti-angiogenic therapies, especially towards vessels that are resistant to VEGF or VEGFR-2 inhibitors."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature07083"xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature07083"xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Shibuya M."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Shibuya M."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Betsholtz C."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Betsholtz C."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Alitalo K."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Alitalo K."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Tammela T."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Tammela T."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Laakkonen P."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Laakkonen P."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Christofori G."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Christofori G."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Duarte A."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Duarte A."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Eichmann A."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Eichmann A."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Yla-Herttuala S."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Yla-Herttuala S."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Hellstrom M."xsd:string |
| http://purl.uniprot.org/citations/18594512 | http://purl.uniprot.org/core/author | "Hellstrom M."xsd:string |