Identification of Hepatocyte Growth Factor Autocrine Loops in Breast Carcinomas: Possible Target for Therapeutic Intervention
Abstract
HGF (also known as scatter factor), and its receptor Met, are over-expressed in invasive human breast cancer. In addition, increased HGF expression and sustained activation of Met have been shown to be important steps in the development of metastatic breast cancer. Therefore, HGF-Met binding is a potential target for anti-cancer antagonists in the treatment of breast cancer metastasis. We have developed an HGF-Met binding assay where Met is immobilized on a plastic plate, followed by the addition of HGF and subsequent detection of HGF binding. Addition of varying compounds/peptides can be monitored for induction of increased or decreased HGF-Met binding. We are using a new technology, known as 'phage display', to isolate short peptides which bind specifically to HGF or Met and block growth factor function. Additionally, we have shown that certain divalent cations (e.g., Cu(2+)) can inhibit HGF-Met binding. Once antagonistic peptides/compounds have been identified, their putative effect on cell functions such as Met activation, cell motility and invasion will be assessed. This approach could lead to the development of novel inhibitors of HGF function in carcinoma cells, and new strategies for improved treatment of breast cancer, perhaps in combination with other anti-cancer agents.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA403383
Entities
People
- Bruce Elliott
- Theodore G. Wright
Organizations
- Queen's University