Accession Number : ADA322230

Title :   Suppression of Vascular Growth in Breast Cancer.

Descriptive Note : Annual rept. 30 Sep 95-1 Oct 96,

Corporate Author : BETH ISRAEL HOSPITAL BOSTON MA

Personal Author(s) : Iruela-Arispe, Louisa

PDF Url : ADA322230

Report Date : OCT 1996

Pagination or Media Count : 16

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-1. 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 aim to understand the molecular mechanism by which TSP-1 mediates endothelial cell apoptosis.

Descriptors :   *CARDIOVASCULAR SYSTEM, *SUPPRESSION, *GROWTH(PHYSIOLOGY), *BREAST CANCER, MOLECULES, PROTEINS, GLYCOPROTEINS, NEOPLASMS, DEOXYRIBONUCLEIC ACIDS, MICE, INHIBITORS, CELLS(BIOLOGY), BLOOD VESSELS, MAMMARY GLANDS, ENDOTHELIUM, CAPILLARIES(ANATOMY), METASTASIS.

Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE