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

Publication ,  Journal Article
Lin, P; Polverini, P; Dewhirst, M; Shan, S; Rao, PS; Peters, K
Published in: J Clin Invest
October 15, 1997

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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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

October 15, 1997

Volume

100

Issue

8

Start / End Page

2072 / 2078

Location

United States

Related Subject Headings

  • Solubility
  • Receptor, TIE-2
  • Receptor Protein-Tyrosine Kinases
  • Rats, Inbred F344
  • Rats
  • Peptide Fragments
  • Neovascularization, Pathologic
  • Mice
  • Mammary Neoplasms, Experimental
  • Immunology
 

Citation

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Chicago
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MLA
NLM
Lin, P., Polverini, P., Dewhirst, M., Shan, S., Rao, P. S., & Peters, K. (1997). Inhibition of tumor angiogenesis using a soluble receptor establishes a role for Tie2 in pathologic vascular growth. J Clin Invest, 100(8), 2072–2078. https://doi.org/10.1172/JCI119740
Lin, P., P. Polverini, M. Dewhirst, S. Shan, P. S. Rao, and K. Peters. “Inhibition of tumor angiogenesis using a soluble receptor establishes a role for Tie2 in pathologic vascular growth.J Clin Invest 100, no. 8 (October 15, 1997): 2072–78. https://doi.org/10.1172/JCI119740.
Lin P, Polverini P, Dewhirst M, Shan S, Rao PS, Peters K. Inhibition of tumor angiogenesis using a soluble receptor establishes a role for Tie2 in pathologic vascular growth. J Clin Invest. 1997 Oct 15;100(8):2072–8.
Lin, P., et al. “Inhibition of tumor angiogenesis using a soluble receptor establishes a role for Tie2 in pathologic vascular growth.J Clin Invest, vol. 100, no. 8, Oct. 1997, pp. 2072–78. Pubmed, doi:10.1172/JCI119740.
Lin P, Polverini P, Dewhirst M, Shan S, Rao PS, Peters K. Inhibition of tumor angiogenesis using a soluble receptor establishes a role for Tie2 in pathologic vascular growth. J Clin Invest. 1997 Oct 15;100(8):2072–2078.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

October 15, 1997

Volume

100

Issue

8

Start / End Page

2072 / 2078

Location

United States

Related Subject Headings

  • Solubility
  • Receptor, TIE-2
  • Receptor Protein-Tyrosine Kinases
  • Rats, Inbred F344
  • Rats
  • Peptide Fragments
  • Neovascularization, Pathologic
  • Mice
  • Mammary Neoplasms, Experimental
  • Immunology