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Cancer Stem Cells
Article first published online: 5 AUG 2009
Copyright © 2009 AlphaMed Press
Volume 27, Issue 10, pages 2405–2413, October 2009
How to Cite
Alvero, A. B., Fu, H.-H., Holmberg, J., Visintin, I., Mor, L., Marquina, C. C., Oidtman, J., Silasi, D.-A. and Mor, G. (2009), Stem-Like Ovarian Cancer Cells Can Serve as Tumor Vascular Progenitors. STEM CELLS, 27: 2405–2413. doi: 10.1002/stem.191
Author contributions: A.A.: performed Matrigel differentiation with specific inhibitors, participated in the design, analysis, coordination of the studies, and drafting the manuscript; H.F.: performed western blots; J.H.: performed in vivo tumor formation, flow cytometry studies, and collection of supernatants for cytokine studies; I.V., L.M., and C.C.M.: prepared tissue sections and performed immunostaining studies; J.O.: performed the initial matrigel differentiation experiments; D.S.: assisted in processing and analysis of tissue sections; G.M.: conceptualized the study, participated in the experimental design, data analysis, and final drafting of the manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS August 5, 2009.
- Issue published online: 13 OCT 2009
- Article first published online: 5 AUG 2009
- Accepted manuscript online: 5 AUG 2009 12:00AM EST
- Manuscript Accepted: 28 JUL 2009
- Manuscript Received: 17 JUN 2009
- NCI/NIH. Grant Numbers: RO1CA127913, RO1CA118678
- The Janet Burros Memorial Foundation
- The Sands Family Foundation
- Discovery To Cure Research Program
- Ovarian cancer;
- Stem cells;
Neovascularization is required for solid tumor maintenance, progression, and metastasis. The most described contribution of cancer cells in tumor neovascularization is the secretion of factors, which attract various cell types to establish a microenvironment that promotes blood vessel formation. The cancer stem cell hypothesis suggests that tumors are composed of cells that may share the differentiation capacity of normal stem cells. Similar to normal stem cells, cancer stem cells (CSCs) have the capacity to acquire different phenotypes. Thus, it is possible that CSCs have a bigger role in the process of tumor neovascularization. In this study, we show the capacity of a specific population of ovarian cancer cells with stem-like properties to give rise to xenograft tumors containing blood vessels, which are lined by human CD34+ cells. In addition, when cultured in high-density Matrigel, these cells mimic the behavior of normal endothelial cells and can form vessel-like structures in 24 hours. Microscopic analysis showed extensive branching and maturation of vessel-like structures in 7 days. Western blot and flow cytometry analysis showed that this process is accompanied by the acquisition of classic endothelial markers, CD34 and VE-cadherin. More importantly, we show that this process is vascular endothelial growth factor–independent, but IKKβ-dependent. Our findings suggest that anti-angiogenic therapies should take into consideration the inherent capacity of these cells to serve as vascular progenitors. STEM CELLS 2009;27:2405–2413