Purpose: Development of new capillary blood vessels is essential for the growth of cancer. Two distinct processes, vasculogenesis and angiogenesis implement the formation of the new vascular network. Recently, it was demonstrated that vasculogenesis creates the primary network of vascular endothelial cells that will become major blood vessels in malignant tumors by the recruitment of CD34(+)/vascular endothelial growth factor receptor 2 (FLK-1)(+ )endothelial progenitor cells (EPCs) to sites of the new vessel formation with subsequent differentiation into mature endothelial cell. Therefore the aim of this study was a) to quantitate EPCs in breast cancer patients and b) to evaluate if the release of EPCs into the circulation is mainly regulated by the tumor himself.
Experimental design: CD34(+)FLK-1(+ )EPCs were measured in the peripheral circulation of patients with breast cancer (n = 47) before and after therapy. Furthermore the potential of EPCs to differentiate into endothelial cells was investigated by late-outgrowth experiments and the metabolic uptake of dil-acetylated-LDL and immunoreactivity against von Willebrand factor.
Results: In breast cancer patients the amount of CD34(+)FLK-1(+ )EPCs (percent of peripheral blood mononuclear cells) is significantly increased in women with breast cancer. Tumors larger than 2 cm showed significantly higher values of CD34(+)FLK-1(+ )EPCs. After excision of the tumor the amount of CD34(+)FLK-1(+ )EPCs rapidly declines.
Conclusions: Our findings lead to the tumor, as source of angiogenic chemokines, is most important for recruiting CD34(+)FLK-1(+ )EPCs during breast cancer development. Therefore circulating endothelial progenitor cells may work as a new diagnostic tool in the screening and diagnosis of breast cancer.