Targeting Tie2 to Increase Breast Cancer Responsiveness to Antiangiogenic Therapy
Abstract
Antiangiogenic therapy of cancers targets their blood vessels in an effort to deprive tumors of oxygen and nutrients. Results from human trials have been poorer than results from mouse testing. This disparity may be explained by more extensive coverage of vessels in human cancers, like breast cancer, by protective periendothelial mesenchymal cells (pericytes), rendering these vessels more therapy resistant. Mouse mammary tumor virus (MMTV) -induced mammary carcinomas reproduce the extensive pericyte coverage of tumor vessels seen in human breast cancers. This project will determine whether inhibiting activation of the endothelial cell Tie2 receptor reduces vessel pericyte coverage in MMTV- induced tumors and improves response to antiangiogenic agents. To do this, we are creating tumors with doxycycline-inducible expression of Tie2Ex, an inhibitor of Tie2 activation. Prior to doing this in mice that develop MMTV-induced mammary carcinomas, which will require transgenic introduction of regulatory components and the Tie2Ex gene, we are first developing and testing doxycycline-inducible Tie2Ex expression in transfectable Kl735 tumors. Progress has been made towards the creation of these tumors and testing can soon begin on the effects of Tie2Ex expression on Kl735 tumor vessel pericyte coverage and response to antiangiogenic therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2004
- Accession Number
- ADA427176
Entities
People
- William M. Lee
Organizations
- University of Pennsylvania