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The development of blood supply is crucial to the growth and progression of breast tumors. However, the contribution and role of endothelial progenitor cells (EPCs) in blood vessel formation in human breast tumors is undefined. Here, we demonstrate for the first time that ~68% of the cells integrated into vasculatures in late stage human breast tumors express CD34 and CD133 (the putative EPC markers). We also demonstrate that metastatic human breast cancer and mouse mammary gland carcinomas (MGCas) aberrantly express granulocyte colony-stimulating factor (G-CSF). Inhibition of the MGCa-derived G-CSF significantly decreased the numbers of EPCs in circulation and tumor vasculatures, as well as microvascular density and growth of transplanted MGCa in mice. These results indicate that EPCs may significantly contribute to blood vessel formation in advanced stage, G-CSF-expressing breast tumors and that patients with GCSF-producing breast tumors may benefit from angiotherapeutic protocols that inhibit G-CSF-mediated neovascularization.

Endothelial Progenitor Cells Significantly Contribute to Vasculatures in Human and Mouse Breast Tumors