Endothelial Cell-Specific Receptor TIE-2 as a Therapeutic Target.
Annual rept. 1 Jul 97-30 Jun 98
GEORGETOWN UNIV WASHINGTON DC
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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.
- Anatomy and Physiology
- Medicine and Medical Research