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

Abstract

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 G-CSF-producing breast tumors may benefit from angiotherapeutic protocols that inhibit G-CSF-mediated neovascularization.

The Canonical NF-κB Pathway Governs Mammary Tumorigenesis in Transgenic Mice and Tumor Stem Cell Expansion

“…G-CSF is produced in advanced human and murine breast cancers (39). Breast tumor derived CSF-1 increased hematopoietic stem cells and endothelial progenitor cell numbers in the mouse (39).…”

“…G-CSF is produced in advanced human and murine breast cancers (39). Breast tumor derived CSF-1 increased hematopoietic stem cells and endothelial progenitor cell numbers in the mouse (39). In prior studies investigating the potential role of macrophages in mammary tumor progression, the polyoma middle T antigen was expressed in the murine mammary gland and the animals crossed with mice expressing a mutation of the CSF-1 receptor (34).…”

Activating Peroxisome Proliferator-Activated Receptor γ Mutant Promotes Tumor Growth In vivo by Enhancing Angiogenesis

“…The antibodies were directed to von Willebrad (vWF) (DAKO, Carpinteria, CA), c-Kit, CD133, and CD31 (BIOCARE Medical, Concord, CA) (24). Heat-induced epitope retrieval was performed on formalin-fixed and paraffin-embedded sections by incubating the sections in citrate buffer with 5% Tween 20 (pH 6.0) at 100°C for 20 minutes and allowed to cool for 20 minutes prior to staining.…”

Nuclear Factor-κB Enhances ErbB2-Induced Mammary Tumorigenesis and Neoangiogenesis in Vivo

“…Our recent studies had suggested an increased abundance of VEGF in the circulation of MMTV-ErbB2 transgenic mice (180 mg/ml versus 43 mg/ml). 41 To determine the NF-B-regulated proteins secreted by NAFA cells, the supernatant of the NAFA and NAFA-I B␣SR were analyzed for secreted chemokines and cytokines using cytokine arrays ( Figure 7A). 34 Subtractive analysis was then conducted to identify NF-B-regulated secreted proteins ( Figure 7B).…”