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Human Bone Marrow-Derived Mesenchymal Stem Cells Suppress Human Glioma Growth Through Inhibition of Angiogenesis.
MedLine Citation:
PMID:  23034897     Owner:  NLM     Status:  Publisher    
Tumor tropism of human bone marrow-derived mesenchymal stem cells (MSC) has been exploited for the delivery of therapeutic genes for anti-cancer therapy. However, the exact contribution of these cells in the tumor microenvironment remains unknown. In this study, we examined the biological effect of MSC on tumor cells. The results showed that MSC inhibited the growth of human glioma cell lines and patient-derived primary glioma cells in vitro. Co-administration of MSC and glioma cells resulted in significant reduction in tumor volume and vascular density, which was not observed when glioma was injected with immortalized normal human astrocytes. Using endothelial progenitor cells (EPC) from healthy donors and HUVEC endothelial cells, the extent of EPC recruitment and capacity to form endothelial tubes was significantly impaired in conditioned media derived from MSC/glioma co-culture, suggesting that MSC suppressed tumor angiogenesis through the released of anti-angiogenic factors. Further studies using antibody array showed reduced expression of platelet derived growth factor (PDGF)-BB and interleukin (IL)-1β in MSC/glioma co-culture when compared with controls. In MSC/glioma co-culture, PDGF-BB mRNA and the corresponding proteins (soluble and membrane bound forms), as well as the receptors were found to be significantly down-regulated when compared with that of glioma co-cultured with normal human astrocytes or glioma monoculture. Furthermore, IL-1β, phosphorylated Akt and cathepsin B proteins were also reduced in MSC/glioma. Taken together, these data indicated that the anti-tumor effect of MSC may be mediated through down-regulation of PDGF/PDGFR axis, which is known to play a key role in glioma angiogenesis.
Ivy Aw Ho; Han C Toh; Wai H Ng; Yuan L Teo; Chang M Guo; Kam M Hui; Paula Yp Lam
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-3
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  -     ISSN:  1549-4918     ISO Abbreviation:  Stem Cells     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 AlphaMed Press.
Laboratory of Cancer Gene Therapy, Humphrey Oei Institute of Cancer Research, National Cancer Center.
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