Linked Life Data

17009333

Source:http://linkedlifedata.com/resource/pubmed/id/17009333

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-3-5
pubmed:abstractText
Heterogeneous metabolic microenvironments in tumors affect local cell growth, survival, and overall therapeutic efficacy. Hypoxia-inducible-factor-1alpha (HIF-1alpha) is a transcription factor that responds to low-oxygen environments by upregulating genes for cell survival and metabolism. To date, the metabolic effects of HIF-1alpha in three-dimensional tissue have not been investigated. Preliminary experiments have shown that the effects of HIF-1alpha are dependent on glucose availability. Based on this observation, we hypothesized that HIF-1alpha would not affect cell survival and metabolism in the center of spheroids, where the concentrations of oxygen and glucose are low, similar to hypoxic regions found in tumors. To test this hypothesis we used fluorescence microscopy and the tumor cylindroid model to quantify cellular viability in three-dimensional tissue. Isotope labeling and metabolic flux analysis were also used to quantity the intracellular metabolism of wild-type and HIF-1alpha-null spheroids. As hypothesized, cell survival and intracellular metabolism were not different between wild-type and HIF-1alpha-null tissues. In addition, small spheroids, which contain less quiescent cells and are less nutritionally limited, were found to have increased carbon flux through the biosynthetic pentose phosphate and pyruvate carboxylase pathways. These results show how nutrient gradients affect cell growth and metabolism in spheroids and suggest that metabolic microenvironment should be taken into account when developing HIF-1alpha-based therapies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-3592
pubmed:author
pubmed:copyrightInfo
(c) 2006 Wiley Periodicals, Inc.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1167-82
pubmed:dateRevised
2011-5-5
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Flux analysis shows that hypoxia-inducible-factor-1-alpha minimally affects intracellular metabolism in tumor spheroids.
pubmed:affiliation
Department of Chemical Engineering, University of Massachusetts, Amherst, 686 North Pleasant Street, Amherst, Massachusetts 01003-9303, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural