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Stem Cell Technology: Epigenetics, Genomics, Proteomics and Metabonomics
Article first published online: 20 AUG 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 9, pages 1831–1841, September 2012
How to Cite
Benayoun, L., Gingis-Velitski, S., Voloshin, T., Segal, E., Segev, R., Munster, M., Bril, R., Satchi-Fainaro, R., Scherer, S. J. and Shaked, Y. (2012), Tumor-Initiating Cells of Various Tumor Types Exhibit Differential Angiogenic Properties and React Differently to Antiangiogenic Drugs. STEM CELLS, 30: 1831–1841. doi: 10.1002/stem.1170
Author contributions: L.B.: conception and design, collection and assembly of the data, and data interpretation; S.G.V., T.V., E.S., R.S., M.M., and R.V.: collection and assembly of data; R.S.F. and S.J.S.: conception and design, data analysis and interpretation, and critical reading of the manuscript; Y.S.: conceptual and design, collection and assembly of data, data analysis and interpretation, financial support, and manuscript writing.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS July 10, 2012.
- Issue published online: 20 AUG 2012
- Article first published online: 20 AUG 2012
- Accepted manuscript online: 10 JUL 2012 04:10PM EST
- Manuscript Accepted: 12 JUN 2012
- Manuscript Received: 3 APR 2012
- Israel Student Education Foundation, Fine, and Jacobs studentships
- Israeli Ministry of Health, Israel Science Foundation, European Commission under FP7 program (Marie Curie)
- Hoffmann La Roche
- Cancer stem cells;
- Bone marrow-derived cells;
Tumor-initiating cells (TICs) are a subtype of tumor cells believed to be critical for initiating tumorigenesis. We sought to determine the angiogenic properties of TICs in different tumor types including U-87MG (glioblastoma), HT29 (colon), MCF7 (breast), A549 (non-small-cell lung), and PANC1 (pancreatic) cancers. Long-term cultures grown either as monolayers (“TIC-low”) or as nonadherent tumor spheres (“TIC-high”) were generated. The TIC-high fractions exhibited increased expression of stem cell surface markers, high aldehyde dehydrogenase activity, high expression of p21, and resistance to standard chemotherapy in comparison to TIC-low fractions. Furthermore, TICs from U-87MG and HT29 but not from MCF7, A549, and PANC1 tumor types possess increased angiogenic activity. Consequently, the efficacy of vascular endothelial growth factor-A (VEGF-A) neutralizing antibody is limited only to those tumors that are dependent on VEGF-A activity. In addition, such therapy had little or reversed antiangiogenic effects on tumors that do not necessarily rely on VEGF-dependent angiogenesis. Differential angiogenic activity and antiangiogenic therapy sensitivity were also observed in TICs of the same tumor type, suggesting redundant angiogenic pathways. Collectively, our results suggest that the efficacy of antiangiogenic drugs is dependent on the angiogenic properties of TICs and, therefore, can serve as a possible biomarker to predict antiangiogenic treatment efficacy. Stem Cells2012;30:1831–1841