Accession Number:

ADA359267

Title:

Endothelial Cell-Specific Receptor TIE-2 as a Therapeutic Target.

Descriptive Note:

Annual rept. 1 Jul 97-30 Jun 98

Corporate Author:

GEORGETOWN UNIV WASHINGTON DC

Personal Author(s):

Report Date:

1998-07-01

Pagination or Media Count:

13.0

Abstract:

The goal of the proposed research is to investigate the possibility of using Tie-2, an endothelial cell- specific receptor tyrosine kinase, as a therapeutic target. The ligand of Tie-2 is the recently described novel factor named angiopoietin-l Ang-l. Ang-l is vital to the development of an organized vasculature during embryonic development. We found earlier that Tie-2 is elevated in tumor neovasculature. We have prepared a fusion toxin consisting of Ang-l and Pseudomonas exotoxin. In addition, we have investigated the expression of Ang- 1 and Tie-2 in human breast cancer clinical specimen, and the possible function of Ang-l as an angiogenic factor. Our data suggest that the Ang-lTie-2 system may play a key role in the angiogenic switch - conversion of cancer cells from a non- angiogenic phenotype to an angiogenic one. Insights into the molecular mechanisms involved will lead to the development of therapies that prevent the switch to an angiogenic phenotype and prevent progression from an in-situ to an invasive carcinoma. We will continue to examine the efficacy of the Ang-1-PE toxin for the treatment of breast cancer in animal models. We will continue to study the role of Ang-lTie-2 system in the angiogenic switch.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE