Downregulation of Focal Adhesion Kinase (FAK) by cord blood stem cells inhibits angiogenesis in glioblastoma.
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.
Department of Cancer Biology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA.
Venkata Ramesh
VR
Dasari
Kiranpreet
K
Kaur
Kiran Kumar
KK
Velpula
Dzung H
DH
Dinh
Andrew J
AJ
Tsung
Sanjeeva
S
Mohanam
Jasti S
JS
Rao
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D015536:Down-Regulation; D005312:Fetal Blood / Q000166:cytology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D005910:Glioma / Q000473:pathology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D014183:Transplantation, Heterologous
D017077:Culture Media, Conditioned; D051416:Focal Adhesion Protein-Tyrosine Kinases