Suppression of Vascular Growth in Breast Cancer
Annual rept. 30 Sep 97-29 Sep 98
BETH ISRAEL HOSPITAL BOSTON MA
Pagination or Media Count:
The growth of solid tumors is strictly dependent on new blood vessel formation. This relationship has led to interest in compoundsdrugs with potential to block blood vessel growth, or angiogenesis, in tumors. Clinical trials are currently underway to assess the efficacy of anti-angiogenic therapy. To date, these trials have met with variable success demonstrating promise in some tumor types and not in others. The failure of these agents to affect a broader spectrum of disease is presumed to relate to differences in tissue types. Such results might indicate that alternative drugs might be better suitable to block angiogenesis of specific tumor types. This proposal focuses on the evaluation of thrombospondin-1 TSP-1 as an anti-angiogenic molecule. In this last year of the proposal, we have found that TSP-1 blocks phosphorylation of MAPK by interfering with the ability of endothelial cells to spread in this substrate. We also found that TSP-1 suppresses focal adhesion kinase phosphorylation and very likely affects endothelial cell migration. Finally, we have continued our screening of functional TSP-1 receptors in endothelial cells derived from both normal and mammary tumors, unlike CD-36, we find that alpha v Beta 3, another reported TSP-1 receptor is expressed at similar levels in both cell types.
- Medicine and Medical Research