Suppression of Vascular Growth in Breast Cancer
Abstract
Metastatic and primary tumor growth are both dependent on neovascularization. One can then predict that restrictions in the vascular supply to tumors could impinge on the expansion and uncontrolled growth of tumor cells. Studies presented in this proposal aim to evaluate the effect of an inhibitor of angiogenesis, thrombospondin-1 (TSP-1), in the growth of mammary tumors. The advantage of TSP- 1 over other vascular inhibitors is that this protein is a natural angiogenic suppressor. TSP-1 is produced by the mammary gland during post-lactation and in fact contributes to the regression of capillaries during mammary gland involution. Therefore, we hypothesized that if effective in the regression of tumors, this molecule might not induce secondary or undesirable side effects. We have just completed two years of studies in this proposal. Our findings are encouraging; specifically, we were able to demonstrate in the lack of TSP-1 (utilizing TSP-1 null animals), neovascularization is significantly higher than in the presence of endogenous TSP-l. Furthermore, increase in the endogenous pool of TSP-1 induces apoptosis in capillary endothelial cells. The overall effect is a reduction in the vascular supply to the mammary gland and to the highly vascularized tumors. Experiments within the next two years of this proposal will alm to understand the molecular mechanism by which TSP- 1 mediates endothelial cell apoptosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 1997
- Accession Number
- ADA344491
Entities
People
- Luisa Iruela-arispe
Organizations
- Beth Israel Deaconess Medical Center