Regulation of Breast Tumor Angiogenesis by Interactive FGFR-Notch Signaling
Abstract
Since tumor cell migration and growth are dependent upon the formation of new blood vessels, it should be possible to manipulate invasive breast carcinoma by the inhibition of angiogenesis. This premise assumes that the restriction of the nutrients derived from blood should sustain the regression of solid tumors in man. Indeed, studies with human breast carcinoma have demonstrated an excellent correlation between tumor size, metastasis and support from the capillary network which comprise the microvasculature. It has also been established that tumor size and metastasis can be regulated by the migration, growth, and differentiation of the endothelial cell, effectors that either repress endothelial cell migration and/or growth or modify endothelial cell differentiation promise to provide new therapies for the clinical management of human angiogenic-dependent diseases. We have recently identified a novel hormone-receptor pathway which is involved in the regulation of angiogenesis. This hormonal signaling pathway is evolutionarily conserved between human and invertebrates and is a major pathway that signals the fate of cells during development. We have also identified the genes that may enable this pathway to be utilized specifically by the endothelial cell and interestingly, these genes are utilized by the mouse mammary tumor virus to manipulate similar events during the viral induction of mammary carcinoma in mice. Indeed, preliminary data suggest that the manipulation of one of these genes in cell culture regulates the migratory phase of the angiogenesis pathway. Thus, support is requested to confirm the hypothesis that Jagged-induced signaling through the endothelial cell-specific Notch-4 receptor antagonizes the chemotactic activity of the proangiogenic fibroblast growth factors. We suggest that these results may ultimately provide new and novel approaches to the clinical management of human breast carcinoma by the regulation of tumor angiogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA377825
Entities
People
- David M. Mann
Organizations
- American Red Cross