Linked Life Data

18351643

Source:http://linkedlifedata.com/resource/pubmed/id/18351643

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2008-4-16
pubmed:abstractText
The hypoxia-responsiveness of the glycolytic machinery may allow pretreatment identification of hypoxic tumors from HIF-1 targets (e.g., Glut-1) or [18F]-fluorodeoxyglucose positron emission tomography but results have been mixed. We hypothesized that this discrepancy is an inevitable consequence of elevated aerobic glycolysis in tumors (Warburg effect) as energetics in predominantly glycolytic cells is little affected by hypoxia. Accordingly, we characterized glycolytic and mitochondrial ATP generation in normoxic and anoxic cell lines. Measurements demonstrated that most cancer cells rely largely on aerobic glycolysis as it accounts for 56-63% of their ATP budget, but in the cervical carcinoma SiHa, ATP synthesis was mainly mitochondrial. Moreover, the stimulatory effect of anoxia on glycolytic flux was inversely correlated to the relative reliance on aerobic glycolysis. Next, tumor cells representing a Warburg or a nonglycolytic phenotype were grown in mice and spatial patterns of hypoxia (pimonidazole-stained), Glut-1 expression and (18)F-FDG uptake were analysed on sectioned tumors. Only in SiHa tumors did foci of elevated glucose metabolism consistently colocalize with regions of hypoxia and elevated Glut-1 expression. In contrast, spatial patterns of Glut-1 and pimonidazole staining correlated reasonably well in all tumors. In conclusion, Glut-1's value as a hypoxia marker is not severely restricted by aerobic glycolysis. In contrast, the specificity of (18)F-FDG uptake and Glut-1 expression as markers of regional hypoxia and glucose metabolism, respectively, scales inversely with the intensity of the Warburg effect. This linkage suggests that multi-tracer imaging combining FDG and hypoxia-specific markers may provide therapeutically relevant information on tumor energetic phenotypes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1097-0215
pubmed:author
pubmed:copyrightInfo
(c) 2008 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
122
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2726-34
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Aerobic glycolysis in cancers: implications for the usability of oxygen-responsive genes and fluorodeoxyglucose-PET as markers of tissue hypoxia.
pubmed:affiliation
Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark. morten@oncology.dk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't