The Role of Fps in Tumor-Associated Angiogenesis
Abstract
Fps and Fer are members of a unique family of cytoplasmic tyrosine kinases. Transgenic expression of Fps in mice (fps(exp MF)) gave rise to hyper-vascularity and multi-focal hemangiomas implicating this kinase in angiogenic regulation. This phenotype suggested that tumorigenesis and metastases may be promoted in these mice and conversely, inhibited in fps loss-of-function mice. Surprisingly, we observed early onset of tumors in fps loss-of-function mice (relative to wild type) suggesting that Fps has a tumor suppressor-like function. Characterization of the vessels in fps(exp MF) mice showed that their vessels were leaky, and that vascularity was increased approximately 1.7-fold. In addition, it was shown that the vascular defects in these mice correlated with VFGF- and PDGF-activation of gain-of-function Fps in endothelial cells. Numerous hematological and hemostatic defects associated with the angiogenic phenotype were also observed. Interestingly, these abnormalities were reminiscent of Kasabach Merritt Syndrome and disseminated intravascular coagulation. Collectively, these data suggested that the vascular abnormalities in fps(exp MF) mice are a result of a defect/delay in vascular maturation. As well, they suggest that Fps influences the processes of angiogenesis and hemostasis through regulatory effects on the endothelium.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2004
- Accession Number
- ADA428164
Entities
People
- Peter A. Greer
- Waheed Sangrar
Organizations
- Queen's University