A Model for Breast Cancer-Induced Angiogenesis

Abstract : Breast tumor growth and development is dependent upon the induction of neovascularization. The specific aims of this proposal define an approach to determine the stage of breast tumor progression in which angiogenesis is induced, to define cellular products which initiate vascular growth, and to develop and test an in vitro model system in which to define the role of multiple cell types in the angiogenic process. In the first two years of this proposal, we examined human tissues at multiple stages of tumor development and quantified vessel formation at each stage. These studies showed that epithelial vascularization begins in the earliest stages of epithelial proliferation. In addition, the vascularity of normal epithelium was greater in cancerous breasts than non-cancerous breasts. We have now examined these tissues by immunohistochemistry and in situ hybridization for numerous angiogenic factors and correlated changes in these factors with the initiation of vessel growth. Finally, we have begun developing the in vitro organ culture system. To date we have defined optimal media conditions and discovered that serine/threonine kinase activity alters epithelial differentiation. We are now in the process of isolating specific cell types from these cultures to examine the regulation of growth factor production in vitro.