Research Paper Volume 2, Issue 11 pp 791—803
Downregulation of Focal Adhesion Kinase (FAK) by cord blood stem cells inhibits angiogenesis in glioblastoma
- 1 Departments of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
- 2 Departments of Neurosurgery, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
Received: October 19, 2010 Accepted: November 4, 2010 Published: November 7, 2010
https://doi.org/10.18632/aging.100217How to Cite
Abstract
Angiogenesis involves the formation of new blood vessels by rerouting or remodeling existing ones and is believed to be the primary method of vessel formation in gliomas. To study the mechanisms by which angiogenesis of glioma cells can be inhibited by human umbilical cord blood stem cells (hUCBSC), we studied two glioma cell lines (SNB19, U251) and a glioma xenograft cell line (5310) alone and in co-culture with hUCBSC. Conditioned media from co-cultures of glioma cells with hUCBSC showed reduced angiogenesis as evaluated by in vitro angiogenesis assay using HMEC cells. Reduction in angiogenesis was associated with downregulation of FAK and integrin αvβ3 in the co-cultures of glioma cells. Downregulation of FAK gene is correlated with downregulation of many angiogenesis-related genes, including Ang1, VEGFA and Akt. Under in vivo conditions, neovascularization by glioma cells was inhibited by hUCBSC. Further, intracranial tumor growth was inhibited by hUCBSC in athymic nude mice. Similar to in vitro results, we observed downregulation of FAK, VEGF and Akt molecules to inhibit angiogenesis in the hUCBSC-treated nude mice brains. Taken together, our results suggest that hUCBSC have the potential to inhibit the angiogenesis of glioma cells both in vitro and in vivo.
Abbreviations
ERK: Extracellular signal-regulated kinases; EGF: Epidermal growth factor; FAK: focal adhesion kinase; FACS: Fluorescence-Activated Cell Sorting; FGF2: Basic fibroblast growth factor; hUCBSC: human umbilical cord blood stem cells; HMEC: Human microvascular endothelial cells; IGF: Insulin-like growth factor; PDGF: Platelet-derived growth factor; VEGF: Vascular endothelial growth factor.