An estimated 30% of breast cancer patients have metastases to the brain and no effective treatment is yet available. Breast cancer brain metastases flourishes under the brain’s highly vascularized microenvironment, which provides nutrients and oxygen to the tumor. The purpose of this study was to analyze the functional properties of endothelial cells derived from metastatic breast cancer to the brain (BBEC). BBEC were isolated from brain tissue specimens of a patient with advanced breast cancer brain metastases. Primary cultures of human BBEC were purified using flow cytometry and characterized as endothelial cells based on positive immunostaining for Factor VIII, CD31, and CD105. BBEC are morphologically larger and more flattened than normal brain endothelial cells (BEC). A functional analysis of BBEC demonstrate that these cells proliferate more slowly than the BEC, and exhibit a significantly higher expression of the proangiogenic growth factors: vascular endothelial growth factor (VEGF), endothelin-1 (Et-1), and interleukin-8 (IL-8), compared to control BEC. Growth factors were identified and quantitated using immunohistochemistry and the enzyme-linked immunosorbent assay. Furthermore, BBEC do not respond to IL-8 stimulation in the migration assay, as do control BEC; and BBEC migrate faster than BEC. These characteristics of BBEC appear to be more similar to primary cultures of human endothelial cells derived from glioma tissue, than normal, control brain endothelial cells. In conclusion, BBEC are phenotypically and functionally distinct from normal endothelial cells, and similar to glioma-derived endothelial cells. Thus the nature of BBEC must be examined in order to appropriately target the tumor vasculature for antiangiogenic therapy.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]