RGD Reference Report - Inhibition of tumor angiogenesis using a soluble receptor establishes a role for Tie2 in pathologic vascular growth. - Rat Genome Database

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Inhibition of tumor angiogenesis using a soluble receptor establishes a role for Tie2 in pathologic vascular growth.

Authors: Lin, P  Polverini, P  Dewhirst, M  Shan, S  Rao, PS  Peters, K 
Citation: Lin P, etal., J Clin Invest. 1997 Oct 15;100(8):2072-8.
RGD ID: 1601511
Pubmed: PMID:9329972   (View Abstract at PubMed)
PMCID: PMC508398   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI119740   (Journal Full-text)

Tie2 is a novel receptor tyrosine kinase that is expressed almost exclusively by vascular endothelium. Disruption of Tie2 function in transgenic mice resulted in embryonic lethality secondary to characteristic vascular defects; similar defects occurred after disruption of the Tie2 ligand. These findings indicate that the Tie2/Tie2 ligand pathway plays important roles during development of the embryonic vasculature. To determine whether the Tie2 pathway was involved in pathologic angiogenesis in adult tissues, a soluble form of the extracellular domain of murine Tie2 (ExTek.6His) was developed and used as a Tie2 inhibitor. After a single application of the ExTek.6His protein into a rat cutaneous window chamber, growth of a mammary tumor inside the chamber was reduced by > 75% (P < 0.005), and tumor vascular length density was reduced by 40% when compared with control-treated tumors (P < 0.01). In the rat cornea, ExTek.6His blocked angiogenesis stimulated by tumor cell conditioned media. ExTek.6His protein did not affect the viability of cultured tumor cells, indicating that the antitumor effect of ExTek.6His was due to the inhibition of tumor angiogenesis. These data demonstrate a role for the Tie2 pathway in pathologic angiogenesis, suggesting that targeting this pathway may yield effective antiangiogenic agents for treatment of cancer and other angiogenic diseases.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of angiogenesis  IMP 1601511 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tek  (TEK receptor tyrosine kinase)


Additional Information