Prevention of the Angiogenic Switch in Human Breast
Abstract
Our overall goal is to determine if human breast cancer can be prevented from becoming angiogenic when it is still at a microscopic size (< ~ 1 mm3). To date we have made the following progress: (1) We have cloned three different human breast cancers that undergo the angiogenic switch at predictable times. (2) We have found that the angiogenic switch time is modified by host stroma: two-fold earlier for tumors in the mammary fat pad, compared to tumors implanted in subcutaneous tissue. (3) We have found that the angiogenic switch is preceded by repression of stromal expression of thrombospodin-1. Angiogenic tumor cells continue to secrete a novel thrombospondin-1 repressing factor. This protein has been purified and partially sequenced. (4) For one of the breast cancers, the angiogenic switch can be detected at a microscopic size by a significant increase in bFGF in platelet alpha granules. (5) We have determined that the BRCA1 gene (breast cancer susceptibility gene), appears to regulate a ratio of thromobospondin-1 to VEGF in breast cancer cells. The lower the thrombospondin-1/VEGF ratio, the sooner the tumor cells will spontaneously switch to the angiogenic phenotype and grow large tumors in SCID mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2007
- Accession Number
- ADA471014
Entities
People
- Judah Folkman