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Research Article Free access | 10.1172/JCI119740

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

P Lin, P Polverini, M Dewhirst, S Shan, P S Rao, and K Peters

Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.

Find articles by Lin, P. in: JCI | PubMed | Google Scholar

Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.

Find articles by Polverini, P. in: JCI | PubMed | Google Scholar

Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.

Find articles by Dewhirst, M. in: JCI | PubMed | Google Scholar

Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.

Find articles by Shan, S. in: JCI | PubMed | Google Scholar

Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.

Find articles by Rao, P. in: JCI | PubMed | Google Scholar

Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.

Find articles by Peters, K. in: JCI | PubMed | Google Scholar

Published October 15, 1997 - More info

Published in Volume 100, Issue 8 on October 15, 1997
J Clin Invest. 1997;100(8):2072–2078. https://doi.org/10.1172/JCI119740.
© 1997 The American Society for Clinical Investigation
Published October 15, 1997 - Version history
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Abstract

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.

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