Linked Life Data

19770585

Source:http://linkedlifedata.com/resource/pubmed/id/19770585

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2009-10-19
pubmed:abstractText
Glioblastomas are highly lethal cancers that contain cellular hierarchies with self-renewing cancer stem cells that can propagate tumors in secondary transplant assays. The potential significance of cancer stem cells in cancer biology has been demonstrated by studies showing contributions to therapeutic resistance, angiogenesis and tumor dispersal. We recently reported that physiologic oxygen levels differentially induce hypoxia inducible factor-2alpha (HIF2alpha) levels in cancer stem cells. HIF1alpha functioned in proliferation and survival of all cancer cells but also was activated in normal neural progenitors suggesting a potentially restricted therapeutic index while HIF2alpha was essential in only in cancer stem cells and was not expressed by normal neural progenitors demonstrating HIF2alpha is a cancer stem cell specific target. We now extend these studies to examine the role of hypoxia in regulating tumor cell plasticity. We find that hypoxia promotes the self-renewal capability of the stem and non-stem population as well as promoting a more stem-like phenotype in the non-stem population with increased neurosphere formation as well as upregulation of important stem cell factors, such as OCT4, NANOG and c-MYC. The importance of HIF2alpha was further supported as forced expression of non-degradable HIF2alpha induced a cancer stem cell marker and augmented the tumorigenic potential of the non-stem population. This novel finding may indicate a specific role of HIF2alpha in promoting glioma tumorigenesis. The unexpected plasticity of the non-stem glioma population and the stem-like phenotype emphasizes the importance of developing therapeutic strategies targeting the microenvironmental influence on the tumor in addition to cancer stem cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1551-4005
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3274-84
pubmed:dateRevised
2010-12-3
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype.
pubmed:affiliation
Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, OH, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural