RESEARCH ARTICLE


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



JohnPaul Chizea1, Vernon K. Dailey1, Eric Williams1, Michael D. Johnson1, Richard G. Pestell 2, John O. Ojeifo 1, 3, *
1 Department of Oncology, the Vincent T. Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA and the
2 Departments of Cancer Biology and Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA


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© 2008 Chizea et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Lombardi Comprehensive Cancer Center, New Research Building, Room EG16,3970 Reservoir Road, NW, Washington, DC 20007, USA; Tel: (202) 687-2308; Fax: (202) 687-7505; E-mail: ojeifoj@georgetown.edu


Abstract

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.

Keywords: Vasculogenesis, Angiogenesis, Endothelial progenitor cells, G-CSF, Endothelial cells, Breast cancer.