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

摘要

The development of blood supply is crucial to the growth and progression of breast tumors. However, the contributionand 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 tumorsexpress CD34 and CD133 (the putative EPC markers). We also demonstrate that metastatic human breast cancer andmouse mammary gland carcinomas (MGCas) aberrantly express granulocyte colony-stimulating factor (G-CSF). Inhibitionof the MGCa-derived G-CSF significantly decreased the numbers of EPCs in circulation and tumor vasculatures, aswell as microvascular density and growth of transplanted MGCa in mice. These results indicate that EPCs may significantlycontribute 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.