Estradiol-mediated tumor neo-vascularization.

Neo-vascularization is essential for tumor growth and metastasis and is presumably initiated by bone marrow-derived endothelial progenitor cells (BM-EPCs). These cells predominantly reside in the bone marrow and are recruited at sites of inflammation, tissue damage and tumors. The tissue-specific factors responsible for recruitment of BM-EPCs and neo-vascularization are the subject of intense investigation. Using bone marrow cells from Tek/green fluorescent protein (GFP) transgenic mice, we analyzed the effect of estrogen on the mobilization of BM-EPCs to orthotopically implanted cancer cells in estrogen- and non-estrogen-supplemented ovariectomized mice. The donor marrow cells were unique as they were fluorescently tagged, allowing for the tracking of their migration to the tumor tissues. Results showed that GFP + BM-EPCs were incorporated within the tumor vasculature in comparison to the sham injections. Notably, estrogen supplementation enhanced the mobilization of BM-EPCs to the tumor site. This elevation shows that estrogen may affect tumor neo-vascularization by inducing the mobilization of BM-EPCs. Understanding and characterizing the mechanism involved in the estrogen-induced mobilization of BM-EPCs may serve as a 'Trojan horse' in the delivery of bio-molecules that may disrupt tumor vasculogenesis and induce the targeted killing of tumor cells.