Targeting of the Hepatocyte Growth Factor Pathway for the Treatment of Breast Cancer
Abstract
Hepatocyte growth factor (HGF) induces cell growth and cell movement and promotes tumor invasiveness. HGF is produced by fibroblasts within lung tumors, while its' receptor, the c-Met protein, is expressed on the breast tumor cells themselves. High levels of HGF expression correlate with an aggressive tumor phenotype. Expression of the c-Met protein by breast cancer cells in culture also correlates with an estrogen negative phenotype and with loss of estrogen-dependent cell growth. Thus the HGF-c-Met ligand-receptor system may be important in controlling cell growth in breast tumors that have escaped estrogen regulation, a common occurrence in breast cancer patients who fail anti-estrogen therapy. The hypothesis to be tested in this Idea Grant is that interruption of the HGF-c-Met signaling pathway will inhibit growth of estrogen-independent human breast cancer cells and could be a useful therapeutic strategy for breast cancer patients who fail endocrine therapy. We will use two approaches for these studies. (1) an anti-sense strategy that uses vectors constructed in the u6 RNA expression plasmid and delivered by cationic liposomes and (2) a recombinant HGF antagonist molecule (truncated HGF/tHGF) produced in baculovirus and delivered through injection to the peritumoral area.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADB286597
Entities
People
- Jill M. Siegfried
Organizations
- University of Pittsburgh