Flt-1 (VEGFR-1) as an Angiogenic Inhibitor: Implications for a Novel Breast Cancer Therapy
Abstract
Breast cancer progression is dependent on the ability of breast tumors to recruit new blood vessels by angiogenesis. At the level of cell biology, angiogenesis is the migration and proliferation of endothelial cells to form vascular sprouts. These hallmarks of angiogenic endothelial cell biology are conserved between cancer angiogenesis and embryonic angiogenesis. Thus, understanding the molecular cues that regulate the migration and proliferation of endothelial cells during embryonic vascular development has the potential to elucidate novel breast cancer therapies. This proposal involves the analysis of the fit-1 gene, a presumptive negative regulator of vascular outgrowth during embryonic development. To date, we have shown that fit-1 functions to limit endothelial cell numbers during embryonic vascular development by negatively regulating endothelial cell proliferation both in vivo and in vitro. Furthermore, we have demonstrated that the vascular overgrowth phenotype of fit-1 null mutant embryonic stem cell cultures can be partially rescued by co-culturing fit-J null mutant ES cells with wild type ES cells and by treatment of fit-I null mutant ES cultures with a soluble version of the fit-l receptor. These data indicate that fit-l regulates embryonic angiogenesis and suggest a potential therapeutic role for fit-l in regulating the pathological angiogenesis that is essential for breast cancer progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA417967
Entities
People
- Joseph B. Kearney
- Victoria L. Bautch
Organizations
- University of North Carolina at Chapel Hill