The Role of Fps in Tumor-Associated Angiogenesis
Abstract
The tyrosine kinase Fps has been implicated in angiogenesis. Expression of activated Fps - (MFps) causes hyper-vascularity in mice (fpsMF mice) suggesting that Fps may regulate angiogenesis. Studies have shown that the magnitude of vascularity is elevated l.7-fold and is highly-disorganized and tortuous in nature. Stimulation of endothelial cells (EC) isolated from these mice has shown that MFps, but not Eps is activated in response to PDGF and VEGF. This suggests that MFps mediates hyper-sensitization of EC to these growth factors, an abnormality which may underlie the proangiogenic phenotype in these mice. In other studies we have shown early tumor onset in the context of loss-of-function Eps genetic backgrounds suggesting that Fps may behave as a tumor suppressor. Thus, Eps may be a suitable target for the development of anti-tumorigenic and anti-angiogenic therapeutics. Lastly, fpsMT mice may have a DIC-like phenotype. This was suggested by hemostatic defects and by an array of phenotypic features characteristic of disorders associated with vascular hyperplasia. This is an important finding, since DIC occurs as a lethal complication in advanced cancers, including those of the breast.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA418816
Entities
People
- Waheed Sangrar
Organizations
- Queen's University