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A Model for Breast Cancer-Induced Angiogenesis
Annual rept. 1 Sep 1997-31 Aug 1998
CINCINNATI UNIV OH
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Tumor growth is absolutely dependent upon angiogenesis. Prior to the development of breast cancer, the breast tissue in many women undergoes progressive changes, which include proliferative breast disease and carcinoma in situ. We examined these pathologic changes for the level of vascularity and the presence of angiogenic growth factors in the hopes of identifying targets for chemoprophylaxis. To date, we have shown that angiogenesis begins in the earliest stages of progression. In addition, even normal breast tissue contains a complex mixture of angiogenic factors that increase in the epithelium, stroma, or infiltrating leukocytes during progression to invasive breast cancer. Using an in vitro organ culture system of normal breast tissue, we found that exogenous angiogenic factors were unable to stimulate endothelial cell proliferation. Furthermore, under non-stimulated conditions, endothelial cell proliferation was restricted to the adipose tissue and perilobular connective tissue. The endothelium within the fibrous stroma could almost never be induced to proliferate. The stroma of normal breast tissue is able to inhibit endothelial cell proliferation under some conditions. Therefore, the angiogenic potential in this tissue appears to be the result of an interplay of angiogenic stimulators and inhibitors.
APPROVED FOR PUBLIC RELEASE